Journal articles: 'Structure and Dynamics of Peptides by NMR Spectroscopy'

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Siminovitch, David J. "Solid-state NMR studies of proteins: the view from static 2H NMR experiments." Biochemistry and Cell Biology 76, no. 2-3 (May 1, 1998): 411–22. http://dx.doi.org/10.1139/o98-054.

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The application of solid-state 2H NMR spectroscopy to the study of protein and peptide structure and dynamics is reviewed. The advantages of solid-state NMR for the study of proteins are considered, and the particular advantages of solid-state 2H NMR are summarized. Examples of work on the integral membrane protein bacteriorhodopsin, and the membrane peptide gramicidin, are used to highlight the major achievements of the 2H NMR technique. These examples demonstrate that through the use of oriented samples, it is possible to obtain both structural and dynamic information simultaneously.Key words: solid-state NMR, 2H NMR, membrane peptides, membrane proteins, oriented bilayers.

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Ader, C., R. Schneider, K. Seidel, M. Etzkorn, and M. Baldus. "Magic-angle-spinning NMR spectroscopy applied to small molecules and peptides in lipid bilayers." Biochemical Society Transactions 35, no. 5 (October 25, 2007): 991–95. http://dx.doi.org/10.1042/bst0350991.

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ssNMR (solid-state NMR) spectroscopy provides increasing possibilities to study the structural and dynamic aspects of biological membranes. Here, we review recent ssNMR experiments that are based on MAS (magic angle spinning) and that provide insight into the structure and dynamics of membrane systems at the atomic level. Such methods can be used to study membrane architecture, domain formation or molecular complexation in a way that is highly complementary to other biophysical methods such as imaging or calorimetry.

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Hong, Mei. "Structure, Topology, and Dynamics of Membrane Peptides and Proteins from Solid-State NMR Spectroscopy." Journal of Physical Chemistry B 111, no. 35 (September 2007): 10340–51. http://dx.doi.org/10.1021/jp073652j.

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POLYANSKY, ANTON A., PAVEL E. VOLYNSKY, and ROMAN G. EFREMOV. "COMPUTER SIMULATIONS OF MEMBRANE-LYTIC PEPTIDES: PERSPECTIVES IN DRUG DESIGN." Journal of Bioinformatics and Computational Biology 05, no. 02b (April 2007): 611–26. http://dx.doi.org/10.1142/s0219720007002783.

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Structure activity relationships were investigated for membrane-lytic peptides (MLP) Ltc1 and Ltc2a from the latarcin family. The peptides were studied via long-term molecular dynamics (MD) simulations in different membrane environments (detergent micelles, mixed lipid bilayers mimiking eukaryotic and bacterial membranes). The calculated structure of Ltc2a in sodium dodecyl sulfate micelle agrees well with the data obtained by 1H-NMR spectroscopy. This validates the applied modeling approach. The binding mode of MLPs is governed by several factors: (i) the membrane surface curvature; (ii) the conformational plasticity and hydrophobic organization of the peptide, which depend on the arrangement of charged, non-polar and helix-breaking residues in the amino acid sequence. In contrast to Ltc1, insertion of Ltc2a into model membranes induces significant changes in dynamic behavior of lipids in the contact region. Such a prominent membrane destabilization correlates with high membrane-lytic activity of Ltc2a. In all cases the "membrane response" has a local character and is caused by formation of specific peptide-lipid contacts. Results of MD simulations of Ltc2a in model membranes were used to develop a number of its analogs with predefined activity.

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BUCK, MATTHIAS. "Trifluoroethanol and colleagues: cosolvents come of age. Recent studies with peptides and proteins." Quarterly Reviews of Biophysics 31, no. 3 (August 1998): 297–355. http://dx.doi.org/10.1017/s003358359800345x.

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Alcohol based cosolvents, such as trifluoroethanol (TFE) have been used for many decades to denature proteins and to stabilize structures in peptides. Nuclear magnetic resonance spectroscopy and site directed mutagenesis have recently made it possible to characterize the effects of TFE and of other alcohols on polypeptide structure and dynamics at high resolution. This review examines such studies, particularly of hen lysozyme and β-lactoglobulin. It presents an overview of what has been learnt about conformational preferences of the polypeptide chain, the interactions that stabilize structures and the nature of the denatured states. The effect of TFE on transition states and on the pathways of protein folding and unfolding are also reviewed. Despite considerable progress there is as yet no single mechanism that accounts for all of the effects TFE and related cosolvents have on polypeptide conformation. However, a number of critical questions are beginning to be answered. Studies with alcohols such as TFE, and ‘cosolvent engineering’ in general, have become valuable tools for probing biomolecular structure, function and dynamics.1. COSOLVENTS: OLD HAT? 2982. HOW DOES TFE WORK? 2992.1 Effect on hydrogen bonding 3002.2 Effect on non-polar sidechains 3012.3 Effect on solvent structure 3023. EFFECTS OF TFE ON (UN-)FOLDING TRANSITIONS 3033.1 Pretransition 3033.2 Transition 3043.3 Posttransition 3053.4 Far UV CD spectroscopic detection of structure 3063.5 Effect with temperature 3063.6 Effect with additional denaturants 3064. THERMODYNAMIC PARAMETERS FROM STRUCTURAL TRANSITIONS OF PEPTIDES AND PROTEINS IN TFE 3075. ADVANCES IN NMR SPECTROSCOPY 3105.1 Chemical shifts 3105.2 3[Jscr ]HNHαcoupling constants 3115.3 Amide hydrogen exchange 3125.4 Nuclear Overhauser Effects (NOEs) 3126. α-HELIX – EVERYWHERE? 3136.1 Intrinsic helix propensity equals helix content? 3136.2 A helix propensity scale for the amino acids in TFE 3146.3 Capping motifs and stop signals 3156.4 Limits and population of helices as seen by CD and NMR 3167. TURNS 3178. β-HAIRPINS AND SHEETS 3179. ‘CLUSTERS’ OF SIDECHAINS 32010. THE TFE DENATURED STATE OF β-LACTOGLOBULIN 32111. THE TFE DENATURED STATE OF HEN LYSOZYME 32412. TERTIARY STRUCTURE, DISULPHIDES, DYNAMICS AND COMPACTNESS 32713. PROSPECTS FOR STRUCTURE CALCULATION 32814. EFFECT OF TFE ON QUATERNARY STRUCTURE 32915. EFFECT ON TFE ON UN- AND REFOLDING KINETICS 33016. OTHER USES 33616.1 Mimicking membranes and protein receptors 33616.2 Solubilizing peptides and proteins 33616.3 Cosolvents as helpers for protein folding? 33816.4 Modifying protein dynamics and catalysis 33816.5 Effects on nucleic acids 33916.6 Effects on lipid bilayers and micelles 33916.7 Future applications 33917. CONCLUSIONS: TFE – WHAT IS IT GOOD FOR? 34018. ACKNOWLEDGMENTS 34019. REFERENCES 340

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Krishnan, V. V., Timothy Bentley, Alina Xiong, and Kalyani Maitra. "Conformational Ensembles by NMR and MD Simulations in Model Heptapeptides with Select Tri-Peptide Motifs." International Journal of Molecular Sciences 22, no. 3 (January 29, 2021): 1364. http://dx.doi.org/10.3390/ijms22031364.

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Both nuclear magnetic resonance (NMR) and molecular dynamics (MD) simulations are routinely used in understanding the conformational space sampled by peptides in the solution state. To investigate the role of single-residue change in the ensemble of conformations sampled by a set of heptapeptides, AEVXEVG with X = L, F, A, or G, comprehensive NMR, and MD simulations were performed. The rationale for selecting the particular model peptides is based on the high variability in the occurrence of tri-peptide E*L between the transmembrane β-barrel (TMB) than in globular proteins. The ensemble of conformations sampled by E*L was compared between the three sets of ensembles derived from NMR spectroscopy, MD simulations with explicit solvent, and the random coil conformations. In addition to the estimation of global determinants such as the radius of gyration of a large sample of structures, the ensembles were analyzed using principal component analysis (PCA). In general, the results suggest that the -EVL- peptide indeed adopts a conformational preference that is distinctly different not only from a random distribution but also from other peptides studied here. The relatively straightforward approach presented herein could help understand the conformational preferences of small peptides in the solution state.

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Jobin, Marie-Lise, Lydie Vamparys, Romain Deniau, Axelle Grélard, Cameron Mackereth, Patrick Fuchs, and Isabel Alves. "Biophysical Insight on the Membrane Insertion of an Arginine-Rich Cell-Penetrating Peptide." International Journal of Molecular Sciences 20, no. 18 (September 9, 2019): 4441. http://dx.doi.org/10.3390/ijms20184441.

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Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied. Herein, we investigated the membrane insertion of RW16 into zwitterionic membranes, a versatile CPP that also presents antibacterial and antitumor activities. Using complementary approaches, including NMR spectroscopy, fluorescence spectroscopy, circular dichroism, and molecular dynamic simulations, we determined the high-resolution structure of RW16 and measured its membrane insertion and orientation properties into zwitterionic membranes. Altogether, these results contribute to explaining the versatile properties of this peptide toward zwitterionic lipids.

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Sinelnikova, Anna, and David van der Spoel. "NMR refinement and peptide folding using the GROMACS software." Journal of Biomolecular NMR 75, no. 4-5 (March 28, 2021): 143–49. http://dx.doi.org/10.1007/s10858-021-00363-z.

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AbstractNuclear magnetic resonance spectroscopy is used routinely for studying the three-dimensional structures and dynamics of proteins and nucleic acids. Structure determination is usually done by adding restraints based upon NMR data to a classical energy function and performing restrained molecular simulations. Here we report on the implementation of a script to extract NMR restraints from a NMR-STAR file and export it to the GROMACS software. With this package it is possible to model distance restraints, dihedral restraints and orientation restraints. The output from the script is validated by performing simulations with and without restraints, including the ab initio refinement of one peptide.

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Bechinger, Burkhard. "The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy." Biochimica et Biophysica Acta (BBA) - Biomembranes 1462, no. 1-2 (December 1999): 157–83. http://dx.doi.org/10.1016/s0005-2736(99)00205-9.

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O’Connor, Casey, Kate L. White, Nathalie Doncescu, Tatiana Didenko, Bryan L. Roth, Georges Czaplicki, Raymond C. Stevens, Kurt Wüthrich, and Alain Milon. "NMR structure and dynamics of the agonist dynorphin peptide bound to the human kappa opioid receptor." Proceedings of the National Academy of Sciences 112, no. 38 (September 8, 2015): 11852–57. http://dx.doi.org/10.1073/pnas.1510117112.

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The structure of the dynorphin (1–13) peptide (dynorphin) bound to the human kappa opioid receptor (KOR) has been determined by liquid-state NMR spectroscopy. 1H and 15N chemical shift variations indicated that free and bound peptide is in fast exchange in solutions containing 1 mM dynorphin and 0.01 mM KOR. Radioligand binding indicated an intermediate-affinity interaction, with a Kd of ∼200 nM. Transferred nuclear Overhauser enhancement spectroscopy was used to determine the structure of bound dynorphin. The N-terminal opioid signature, YGGF, was observed to be flexibly disordered, the central part of the peptide from L5 to R9 to form a helical turn, and the C-terminal segment from P10 to K13 to be flexibly disordered in this intermediate-affinity bound state. Combining molecular modeling with NMR provided an initial framework for understanding multistep activation of a G protein-coupled receptor by its cognate peptide ligand.

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Shao, Qing, Kong M. Wong, Dillon T. Seroski, Yiming Wang, Renjie Liu, Anant K. Paravastu, Gregory A. Hudalla, and Carol K. Hall. "Anatomy of a selectively coassembled β-sheet peptide nanofiber." Proceedings of the National Academy of Sciences 117, no. 9 (February 18, 2020): 4710–17. http://dx.doi.org/10.1073/pnas.1912810117.

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Peptide self-assembly, wherein molecule A associates with other A molecules to form fibrillar β-sheet structures, is common in nature and widely used to fabricate synthetic biomaterials. Selective coassembly of peptide pairs A and B with complementary partial charges is gaining interest due to its potential for expanding the form and function of biomaterials that can be realized. It has been hypothesized that charge-complementary peptides organize into alternating ABAB-type arrangements within assembled β-sheets, but no direct molecular-level evidence exists to support this interpretation. We report a computational and experimental approach to characterize molecular-level organization of the established peptide pair, CATCH. Discontinuous molecular dynamics simulations predict that CATCH(+) and CATCH(−) peptides coassemble but do not self-assemble. Two-layer β-sheet amyloid structures predominate, but off-pathway β-barrel oligomers are also predicted. At low concentration, transmission electron microscopy and dynamic light scattering identified nonfibrillar ∼20-nm oligomers, while at high concentrations elongated fibers predominated. Thioflavin T fluorimetry estimates rapid and near-stoichiometric coassembly of CATCH(+) and CATCH(−) at concentrations ≥100 μM. Natural abundance13C NMR and isotope-edited Fourier transform infrared spectroscopy indicate that CATCH(+) and CATCH(−) coassemble into two-component nanofibers instead of self-sorting. However,13C–13C dipolar recoupling solid-state NMR measurements also identify nonnegligible AA and BB interactions among a majority of AB pairs. Collectively, these results demonstrate that strictly alternating arrangements of β-strands predominate in coassembled CATCH structures, but deviations from perfect alternation occur. Off-pathway β-barrel oligomers are also suggested to occur in coassembled β-strand peptide systems.

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Kobchikova, Polina P., Sergey V. Efimov, and Vladimir V. Klochkov. "Binding of Different Cyclosporin Variants to Micelles Evidenced by NMR and MD Simulations." Membranes 13, no. 2 (February 5, 2023): 196. http://dx.doi.org/10.3390/membranes13020196.

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Peptides play a critical role in the life of organisms, performing completely different functions. The biological activity of some peptides, such as cyclosporins, can be determined by the degree of membrane permeability. Thus, it becomes important to study how the molecule interacts with lipid bilayers. Cyclosporins C, E, H and L were characterised molecular dynamics simulation; NMR spectroscopy studies were also carried out for cyclosporins C and E. The comparison of one- and two-dimensional spectra revealed certain similarities between spatial structures of the studied cyclosporin variants. Upon dissolving in water containing DPC micelles, which serve as model membranes, subtle changes in the NMR spectra appear, but in a different way for different cyclosporins. In order to understand whether observed changes are related to any structural modifications, simulation of the interaction of the peptide with the phospholipid micelle was performed. The onset of the interaction was observed, when the peptide is trapped to the surface of the micelle. Simulations of this kind are also of interest in the light of the well-known membrane permeability of cyclosporin, which is important for its biological action.

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Huster, Daniel. "Investigations of the structure and dynamics of membrane-associated peptides by magic angle spinning NMR." Progress in Nuclear Magnetic Resonance Spectroscopy 46, no. 2-3 (May 2005): 79–107. http://dx.doi.org/10.1016/j.pnmrs.2005.01.001.

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Trzepałka, Emilia, Marta Oleszczuk, Maciej Maciejczyk, and Bernard Lammek. "Solution structure of conformationally restricted vasopressin analogues." Acta Biochimica Polonica 51, no. 1 (March 31, 2004): 33–49. http://dx.doi.org/10.18388/abp.2004_3594.

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In recent years, a massive effort has been directed towards designing potent and selective antagonists of neurohypophyseal hormones substituted at position 3. Modification of vasopressin at position 3 with 4,4'-biphenylalanine results in pharmacologically inactive analogues. Chemically, this substitution appears to vary only slightly from those previously made by us (1-Nal or 2-Nal), which afforded potent agonists of V(2) receptors. In this situation, it seemed worthwhile to study the structure of the analogues with 4,4'-biphenylalanine (BPhe) at position 3 in aqueous solution using NMR spectroscopy and total conformational analysis. This contribution is part of extensive studies aimed at understanding spatial structures of 3-substituted [Arg(8)]vasopressin analogues of different pharmacological properties. NMR data were used to calculate 3D structures for all the analogues using two methods, EDMC with the ECEPP/3 force field, and molecular dynamic with the simulated annealing (SA) algorithm. The structures obtained by the first method show a better fit between the NMR spectral evidence and the calculation for all the peptides.

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YOUNG, Helen, Vikram ROONGTA, Thomas J. DALY, and Kevin H. MAYO. "NMR structure and dynamics of monomeric neutrophil-activating peptide 2." Biochemical Journal 338, no. 3 (March 8, 1999): 591–98. http://dx.doi.org/10.1042/bj3380591.

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Neutrophil-activating peptide 2 (NAP-2), which demonstrates a range of proinflammatory activities, is a 72-residue protein belonging to the α-chemokine family. Although NAP-2, like other α-chemokines, is known to self-associate into dimers and tetramers, it has been shown that the monomeric form is physiologically active. Here we investigate the solution structure of monomeric NAP-2 by multi-dimensional 1H-NMR and 15N-NMR spectroscopy and computational modelling. The NAP-2 monomer consists of an amphipathic, triple-stranded, anti-parallel β-sheet on which is folded a C-terminal α-helix and an aperiodic N-terminal segment. The backbone fold is essentially the same as that found in other α-chemokines. 15N T1, T2 and nuclear Overhauser effects (NOEs) have been measured for backbone NH groups and used in a model free approach to calculate order parameters and conformational exchange terms that map out motions of the backbone. N-terminal residues 1 to 17 and the C-terminus are relatively highly flexible, whereas the β-sheet domain forms the most motionally restricted part of the fold. Conformational exchange occurring on the millisecond time scale is noted at the top of the C-terminal helix and at proximal residues from β-strands 1 and 2 and the connecting loop. Dissociation to the monomeric state is apparently responsible for increased internal mobility in NAP-2 compared with dimeric and tetrameric states in other α-chemokines.

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Scheidt, Holger A., and Daniel Huster. "Structure and Dynamics of the Myristoyl Lipid Modification of Src Peptides Determined by 2H Solid-State NMR Spectroscopy." Biophysical Journal 96, no. 9 (May 2009): 3663–72. http://dx.doi.org/10.1016/j.bpj.2009.02.028.

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Bechinger, B. "ChemInform Abstract: The Structure, Dynamics, and Orientation of Antimicrobial Peptides in Membranes by Multidimensional Solid-State NMR Spectroscopy." ChemInform 31, no. 20 (June 8, 2010): no. http://dx.doi.org/10.1002/chin.200020298.

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Weber, Daniel K., and Gianluigi Veglia. "A Theoretical Assessment of the Structure Determination of Multi-Span Membrane Proteins by Oriented Sample Solid-State NMR Spectroscopy." Australian Journal of Chemistry 73, no. 3 (2020): 246. http://dx.doi.org/10.1071/ch19307.

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Oriented sample solid-state NMR (OS-ssNMR) spectroscopy allows the direct determination of the structure and topology of membrane proteins reconstituted into aligned lipid bilayers. Although OS-ssNMR theoretically has no upper size limit, its application to multi-span membrane proteins has not been established because most studies have been restricted to single- or dual-span proteins and peptides. Here, we present a critical assessment of the application of this method to multi-span membrane proteins. We used molecular dynamics simulations to back-calculate [15N-1H] separated local field (SLF) spectra from a G protein-coupled receptor (GPCR) and show that fully resolved spectra can be obtained theoretically for a multi-span membrane protein with currently achievable resonance linewidths.

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Karas, John A., David W. Keizer, and Marc-Antoine Sani. "Nuclear Magnetic Resonance Study of the Peptide FRANCESSEPAROVIC." Australian Journal of Chemistry 73, no. 3 (2020): 158. http://dx.doi.org/10.1071/ch19357.

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As an eminent ambassador of STEM and renowned NMR spectroscopist, Frances Separovic is an internationally famous name, but could it also be a valuable membrane-active peptide sequence? Her name has been used as an amino acid sequence (FS), successfully synthesised, oxidised, and put into contact with membrane models to investigate any serendipitous activity. The 3D structure of the cyclic FS was determined in dodecylphosphocholine (DPC) micelles by solution NMR spectroscopy. FS displayed a twisted bend separating a helical stretch and an unstructured segment. Using solid-state NMR spectroscopy, the effect of FS on 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phosphoserine (DMPS) lipid bilayers was studied. FS did not strongly disturb the neutral membrane surface but likely inserted into their hydrophobic core without a strong effect on the lipid dynamics, while perturbation of the negatively charged membranes remained at the headgroup interface with a strong effect on the lipid dynamics. This study demonstrated that FS is a candidate for discovering potential future therapeutic activities.

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Sinnaeve, Davy, Abir Ben Bouzayene, Emile Ottoy, Gert-Jan Hofman, Eva Erdmann, Bruno Linclau, Ilya Kuprov, José C. Martins, Vladimir Torbeev, and Bruno Kieffer. "Fluorine NMR study of proline-rich sequences using fluoroprolines." Magnetic Resonance 2, no. 2 (November 9, 2021): 795–813. http://dx.doi.org/10.5194/mr-2-795-2021.

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Abstract. Proline homopolymer motifs are found in many proteins; their peculiar conformational and dynamic properties are often directly involved in those proteins' functions. However, the dynamics of proline homopolymers is hard to study by NMR due to a lack of amide protons and small chemical shift dispersion. Exploiting the spectroscopic properties of fluorinated prolines opens interesting perspectives to address these issues. Fluorinated prolines are already widely used in protein structure engineering – they introduce conformational and dynamical biases – but their use as 19F NMR reporters of proline conformation has not yet been explored. In this work, we look at model peptides where Cγ-fluorinated prolines with opposite configurations of the chiral Cγ centre have been introduced at two positions in distinct polyproline segments. By looking at the effects of swapping these (4R)-fluoroproline and (4S)-fluoroproline within the polyproline segments, we were able to separate the intrinsic conformational properties of the polyproline sequence from the conformational alterations instilled by fluorination. We assess the fluoroproline 19F relaxation properties, and we exploit the latter in elucidating binding kinetics to the SH3 (Src homology 3) domain.

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Wang, Guangshun. "Structure, dynamics and mapping of membrane-binding residues of micelle-bound antimicrobial peptides by natural abundance 13C NMR spectroscopy." Biochimica et Biophysica Acta (BBA) - Biomembranes 1798, no. 2 (February 2010): 114–21. http://dx.doi.org/10.1016/j.bbamem.2009.07.028.

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Jacob, Maik H., Roy N. D’Souza, Alexandra I. Lazar, and Werner M. Nau. "Diffusion-Enhanced Förster Resonance Energy Transfer in Flexible Peptides: From the Haas-Steinberg Partial Differential Equation to a Closed Analytical Expression." Polymers 15, no. 3 (January 30, 2023): 705. http://dx.doi.org/10.3390/polym15030705.

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In the huge field of polymer structure and dynamics, including intrinsically disordered peptides, protein folding, and enzyme activity, many questions remain that cannot be answered by methodology based on artificial intelligence, X-ray, or NMR spectroscopy but maybe by fluorescence spectroscopy. The theory of Förster resonance energy transfer (FRET) describes how an optically excited fluorophore transfers its excitation energy through space to an acceptor moiety—with a rate that depends on the distance between donor and acceptor. When the donor and acceptor moiety are conjugated to different sites of a flexible peptide chain or any other linear polymer, the pair could in principle report on chain structure and dynamics, on the site-to-site distance distribution, and on the diffusion coefficient of mutual site-to-site motion of the peptide chain. However, the dependence of FRET on distance distribution and diffusion is not defined by a closed analytical expression but by a partial differential equation (PDE), by the Haas-Steinberg equation (HSE), which can only be solved by time-consuming numerical methods. As a second complication, time-resolved FRET measurements have thus far been deemed necessary. As a third complication, the evaluation requires a computationally demanding but indispensable global analysis of an extended experimental data set. These requirements have made the method accessible to only a few experts. Here, we show how the Haas-Steinberg equation leads to a closed analytical expression (CAE), the Haas-Steinberg-Jacob equation (HSJE), which relates a diffusion-diagnosing parameter, the effective donor–acceptor distance, to the augmented diffusion coefficient, J, composed of the diffusion coefficient, D, and the photophysical parameters that characterize the used FRET method. The effective donor–acceptor distance is easily retrieved either through time-resolved or steady-state fluorescence measurements. Any global fit can now be performed in seconds and minimizes the sum-of-square difference between the experimental values of the effective distance and the values obtained from the HSJE. In summary, the HSJE can give a decisive advantage in applying the speed and sensitivity of FRET spectroscopy to standing questions of polymer structure and dynamics.

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Żamojć, Krzysztof, Karolina Streńska, Dariusz Wyrzykowski, Lech Chmurzyński, and Joanna Makowska. "Interactions of Aβ1-42 Peptide and Its Three Fragments (Aβ8-12, Aβ8-13, and Aβ5-16) with Selected Nonsteroidal Drugs and Compounds of Natural Origin." Symmetry 12, no. 10 (September 23, 2020): 1579. http://dx.doi.org/10.3390/sym12101579.

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In the following paper, we present the results of our studies on the interactions of the Aβ1-42 peptide and its three short fragments, namely Aβ5-16 (RHDSGYEVHHQK; HZ1), Aβ8-13 (SGYEVH; HZ2), and Aβ8-12 (SGYEV; HZ3) with selected painkillers (ibuprofen and aspirin) and compounds of natural origin (anabasine and epinephrine). Steady-state fluorescence spectroscopy was used to study the binding properties of the selected systems. Additionally, based on molecular dynamics (MD) calculations supported by NMR-derived restrains, we have proposed the most likely area of the interactions of Aβ1-42 and Aβ5-16 peptides with the investigated compounds. The influence of symmetrically oriented side chains of amino acid residues present in the first part of the Aβ1-42 sequence on the stability of the resulting complexes has been discussed. Finally, the changes in the peptide structures on account of complex formation were analyzed.

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Forneris, Federico, B. Tom Burnley, and Piet Gros. "Ensemble refinement shows conformational flexibility in crystal structures of human complement factor D." Acta Crystallographica Section D Biological Crystallography 70, no. 3 (February 15, 2014): 733–43. http://dx.doi.org/10.1107/s1399004713032549.

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Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or `exosite', region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na+and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na+ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformationviathe self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail.

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Ganicz, Katarzyna. "ChemInform Abstract: Solid State NMR Spectroscopy as a Tool for Investigation of Structure and Dynamics of Amino Acids and Model Peptides." ChemInform 31, no. 43 (October 24, 2000): no. http://dx.doi.org/10.1002/chin.200043299.

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Fritzsch, Jacob, Alexander Korn, Dayana Surendran, Martin Krueger, Holger A. Scheidt, Kaustubh R. Mote, Perunthiruthy K. Madhu, Sudipta Maiti, and Daniel Huster. "Probing the Influence of Single-Site Mutations in the Central Cross-β Region of Amyloid β (1–40) Peptides." Biomolecules 11, no. 12 (December 9, 2021): 1848. http://dx.doi.org/10.3390/biom11121848.

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Amyloid β (Aβ) is a peptide known to form amyloid fibrils in the brain of patients suffering from Alzheimer’s disease. A complete mechanistic understanding how Aβ peptides form neurotoxic assemblies and how they kill neurons has not yet been achieved. Previous analysis of various Aβ40 mutants could reveal the significant importance of the hydrophobic contact between the residues Phe19 and Leu34 for cell toxicity. For some mutations at Phe19, toxicity was completely abolished. In the current study, we assessed if perturbations introduced by mutations in the direct proximity of the Phe19/Leu34 contact would have similar relevance for the fibrillation kinetics, structure, dynamics and toxicity of the Aβ assemblies. To this end, we rationally modified positions Phe20 or Gly33. A small library of Aβ40 peptides with Phe20 mutated to Lys, Tyr or the non-proteinogenic cyclohexylalanine (Cha) or Gly33 mutated to Ala was synthesized. We used electron microscopy, circular dichroism, X-ray diffraction, solid-state NMR spectroscopy, ThT fluorescence and MTT cell toxicity assays to comprehensively investigate the physicochemical properties of the Aβ fibrils formed by the modified peptides as well as toxicity to a neuronal cell line. Single mutations of either Phe20 or Gly33 led to relatively drastic alterations in the Aβ fibrillation kinetics but left the global, as well as the local structure, of the fibrils largely unchanged. Furthermore, the introduced perturbations caused a severe decrease or loss of cell toxicity compared to wildtype Aβ40. We suggest that perturbations at position Phe20 and Gly33 affect the fibrillation pathway of Aβ40 and, thereby, influence the especially toxic oligomeric species manifesting so that the region around the Phe19/Leu34 hydrophobic contact provides a promising site for the design of small molecules interfering with the Aβ fibrillation pathway.

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Patra, Satyajit, Jean-Benoît Claude, Jean-Valère Naubron, and Jérome Wenger. "Fast interaction dynamics of G-quadruplex and RGG-rich peptides unveiled in zero-mode waveguides." Nucleic Acids Research 49, no. 21 (November 17, 2021): 12348–57. http://dx.doi.org/10.1093/nar/gkab1002.

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Abstract G-quadruplexes (GQs), a non-canonical form of DNA, are receiving a huge interest as target sites for potential applications in antiviral and anticancer drug treatments. The biological functions of GQs can be controlled by specifically binding proteins known as GQs binding proteins. Some of the GQs binding proteins contain an arginine and glycine-rich sequence known as RGG peptide. Despite the important role of RGG, the GQs-RGG interaction remains poorly understood. By single molecule measurements, the interaction dynamics can be determined in principle. However, the RGG–GQs interaction occurs at micromolar concentrations, making conventional single-molecule experiments impossible with a diffraction-limited confocal microscope. Here, we use a 120 nm zero-mode waveguide (ZMW) nanoaperture to overcome the diffraction limit. The combination of dual-color fluorescence cross-correlation spectroscopy (FCCS) with FRET is used to unveil the interaction dynamics and measure the association and dissociation rates. Our data show that the RGG–GQs interaction is predominantly driven by electrostatics but that a specific affinity between the RGG sequence and the GQs structure is preserved. The single molecule approach at micromolar concentration is the key to improve our understanding of GQs function and develop its therapeutic applications by screening a large library of GQs-targeting peptides and proteins.

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Metcalf, Douglas G., Joseph M. Kielec, Kathleen G. Valentine, A. Joshua Wand, William F. DeGrado, and Joel S. Bennett. "NMR Structure of a Disulfide-Crosslinked αIIbβ3 Cytoplasmic Domain Heterodimer." Blood 112, no. 11 (November 16, 2008): 2866. http://dx.doi.org/10.1182/blood.v112.11.2866.2866.

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Abstract The platelet integrin αIIbβ3 is the prototypic example of regulated integrin function. Thus, αIIbβ3 is present in a resting conformation on unstimulated platelets, but switches to an active conformation following platelet stimulation. Recent experiments suggest that disrupting a heteromeric interaction between the αIIb and β3 transmembrane (TM) and cytoplasmic domains shifts αIIbβ3 from its resting to its active conformation. However, structural information about the heteromeric interaction is sparse. Thus far, the structure of the TM heterodimer has only been studied by molecular modeling. Interactions between soluble cytosolic tail peptides have been studied by NMR spectroscopy, but these studies may not reflect native contacts because they fail to account for constraining TM domain interactions. To obtain an NMR structure for the αIIbβ3 cytosolic tail heterodimer that reflects its native structure, we expressed 13C- and 15N-labeled peptides corresponding to αIIb residues 988–1008 and β3 residues 713–762 in E. coli. Residues 987 in αIIb and 712 in β3 were replaced with cysteines, based on modeling that predicts the resultant disulfide bond will fix the peptides in their native orientation. Crosslinked heterodimers were dissolved in dodecylphosphocholine micelles at pH 6.5 and analyzed at 37°C on a 750 MHz NMR spectrometer. Previously, we presented a preliminary analysis of this construct indicating that when constrained by the proximal disulfide bond, the αIIb and β3 cytoplasmic tails interact and the cytosolic tail of β3 consists of three helices. We have now solved the final structure which defines the β3 interface that interacts with the αIIb cytoplasmic tail. The αIIb-β3 heterodimer interface is dynamic, but can be localized to β3 residues 716 and 719 because they have different chemical shifts in the crosslinked heterodimer than they do in the component monomers. This positions β3 residue 723 at the αIIb-β3 interface, consistent with the putative Arg995-Asp723 salt bridge. Interestingly, the αIIb tail is natively unstructured so a static interface for αIIb could not be identified. Additionally, the completed structure defines the relative orientations of the three β3 helices. The β3 cytoplasmic tail contains a sharp kink at residue 724 that fixes the membrane embedded helix (residues 713–723) and the first cytoplasmic helix (residues 725–736) at a right angle. The kink was defined by multiple NMR parameters including NOE distance restraints between residues 721 and 727. The distal cytoplasmic helix (residues 746–757) is related to the rest of the molecule by a flexible loop (residues 737– 745). N15 NOESY-HSQC crosspeak intensities provide evidence that the flexible loop and distal helix undergo increased motion relative to the first two helices, and the final structure reflects this motion because there is no preferred orientation for the distal helix relative to the first two helices. Lastly, the distal helix and flexible loop are joined by β3’s canonical NPXY motif which forms an N-terminal cap for the distal helix. In conclusion, we have solved the NMR structure of a disulfide-crosslinked αIIb/β3 cytoplasmic tail heterodimer. Our analysis indicates that, when constrained by a disulfide bond, the αIIb and β3 cytoplasmic tails interact, providing one mechanism for maintaining αIIbβ3 in a resting state.

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Szutkowski, Kosma, Emilia Sikorska, Iulia Bakanovych, Amrita Roy Choudhury, Andrej Perdih, Stefan Jurga, Marjana Novič, and Igor Zhukov. "Structural Analysis and Dynamic Processes of the Transmembrane Segment Inside Different Micellar Environments—Implications for the TM4 Fragment of the Bilitranslocase Protein." International Journal of Molecular Sciences 20, no. 17 (August 26, 2019): 4172. http://dx.doi.org/10.3390/ijms20174172.

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The transmembrane (TM) proteins are gateways for molecular transport across the cell membrane that are often selected as potential targets for drug design. The bilitranslocase (BTL) protein facilitates the uptake of various anions, such as bilirubin, from the blood into the liver cells. As previously established, there are four hydrophobic transmembrane segments (TM1–TM4), which constitute the structure of the transmembrane channel of the BTL protein. In our previous studies, the 3D high-resolution structure of the TM2 and TM3 transmembrane fragments of the BTL in sodium dodecyl sulfate (SDS) micellar media were solved using Nuclear Magnetic Resonance (NMR) spectroscopy and molecular dynamics simulations (MD). The high-resolution 3D structure of the fourth transmembrane region (TM4) of the BTL was evaluated using NMR spectroscopy in two different micellar media, anionic SDS and zwitterionic DPC (dodecylphosphocholine). The presented experimental data revealed the existence of an α -helical conformation in the central part of the TM4 in both micellar media. In the case of SDS surfactant, the α -helical conformation is observed for the Pro258–Asn269 region. The use of the zwitterionic DPC micelle leads to the formation of an amphipathic α -helix, which is characterized by the extension of the central α -helix in the TM4 fragment to Phe257–Thr271. The complex character of the dynamic processes in the TM4 peptide within both surfactants was analyzed based on the relaxation data acquired on 15 N and 31 P isotopes. Contrary to previously published and present observations in the SDS micelle, the zwitterionic DPC environment leads to intensive low-frequency molecular dynamic processes in the TM4 fragment.

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Nguyen, Leonard T., Paulus H. S. Kwakman, David I. Chan, Zhihong Liu, Leonie de Boer, Sebastian A. J. Zaat, and Hans J. Vogel. "Exploring Platelet Chemokine Antimicrobial Activity: Nuclear Magnetic Resonance Backbone Dynamics of NAP-2 and TC-1." Antimicrobial Agents and Chemotherapy 55, no. 5 (February 14, 2011): 2074–83. http://dx.doi.org/10.1128/aac.01351-10.

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ABSTRACTThe platelet chemokines neutrophil-activating peptide-2 (NAP-2) and thrombocidin-1 (TC-1) differ by only two amino acids at their carboxy-terminal ends. Nevertheless, they display a significant difference in their direct antimicrobial activities, with the longer NAP-2 being inactive and TC-1 being active. In an attempt to rationalize this difference in activity, we studied the structure and the dynamics of both proteins by nuclear magnetic resonance (NMR) spectroscopy. Using15N isotope-labeled protein, we confirmed that the two monomeric proteins essentially have the same overall structure in aqueous solution. However, NMR relaxation measurements provided evidence that the negatively charged carboxy-terminal residues of NAP-2 experience a restricted motion, whereas the carboxy-terminal end of TC-1 moves in an unrestricted manner. The same behavior was also seen in molecular dynamic simulations of both proteins. Detailed analysis of the protein motions through model-free analysis, as well as a determination of their overall correlation times, provided evidence for the existence of a monomer-dimer equilibrium in solution, which seemed to be more prevalent for TC-1. This finding was supported by diffusion NMR experiments. Dimerization generates a larger cationic surface area that would increase the antimicrobial activities of these chemokines. Moreover, these data also show that the negatively charged carboxy-terminal end of NAP-2 (which is absent in TC-1) folds back over part of the positively charged helical region of the protein and, in doing so, interferes with the direct antimicrobial activity.

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Zhao, Yue, Songyi Lin, Ruiwen Yang, Dong Chen, and Na Sun. "Proton Dynamics of Water Diffusion in Shrimp Hydrolysates Flour and Effects of Moisture Absorption on Its Properties." Foods 10, no. 5 (May 20, 2021): 1137. http://dx.doi.org/10.3390/foods10051137.

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Moisture absorbed into shrimp hydrolysates (SHs) flour profoundly affected its properties. The unstored hydrolysate flour was called SHs-0h and SHs stored for 30 h at 25 °C and 75% relative humidity was named SHs-30. During the process of storage, the moisture dynamics in SHs flour were investigated by dynamic vapor sorption (DVS) and low-field nuclear magnetic resonance (LF-NMR). The effects of moisture absorption on the radicals scavenging rates of SHs flour were evaluated by electron paramagnetic resonance (EPR). The effects of moisture absorption on secondary structure were studied by mid-infrared (MIR) spectroscopy and infrared microimaging spectroscopy. The changes of volatile components were monitored by purge and trap coupled with gas chromatography-mass spectrometry (PT-GC-MS). DVS results showed that the moisture absorption rate of SHs flour could reach a maximum of 88.93%. Meanwhile, the water was transformed into more stable water with shorter relaxation times. The porous structure of the SHs-30 h flour disappeared and became smoother compared to SH-0 h flour. DPPH (31.09 ± 0.54%) and OH (26.62 ± 1.14%) radicals scavenging rates of SHs-30 h significantly reduced (p < 0.05) compared to that of SHs-0 h flour. The vibrations of the MIR absorbance peaks were changed. Finally, eight volatile components disappeared and six new volatile compounds were found. This study provided a theory basis for moisture dynamics in peptide flour during the storage process.

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Sheveleva, Nadezhda N., Irina I. Tarasenko, Mikhail A. Vovk, Mariya E. Mikhailova, Igor M. Neelov, and Denis A. Markelov. "NMR Studies of Two Lysine Based Dendrimers with Insertion of Similar Histidine-Arginine and Arginine-Histidine Spacers Having Different Properties for Application in Drug Delivery." International Journal of Molecular Sciences 24, no. 2 (January 4, 2023): 949. http://dx.doi.org/10.3390/ijms24020949.

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In this paper we study two lysine-based peptide dendrimers with Lys-His-Arg and Lys-Arg-His repeating units and terminal lysine groups. Combination of His and Arg properties in a dendrimer could be important for biomedical applications, especially for prevention of dendrimer aggregation and for penetration of dendrimers through various cell membranes. We describe the synthesis of these dendrimers and the confirmation of their structure using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy. NMR spectroscopy and relaxation are used to study the structural and dynamic properties of these macromolecules and to compare them with properties of previously studied dendrimers with Lys-2Arg and Lys-2His repeating units. Our results demonstrate that both Lys-His-Arg and Lys-Arg-His dendrimers have pH sensitive conformation and dynamics. However, properties of Lys-His-Arg at normal pH are more similar to those of the more hydrophobic Lys-2His dendrimer, which has tendency towards aggregation, while the Lys-Arg-His dendrimer is more hydrophilic. Thus, the conformation with the same amino acid composition of Lys-His-Arg is more pH sensitive than Lys-Arg-His, while the presence of Arg groups undoubtedly increases its hydrophilicity compared to Lys-2His. Hence, the Lys-His-Arg dendrimer could be a more suitable (in comparison with Lys-2His and Lys-Arg-His) candidate as a pH sensitive nanocontainer for drug delivery.

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Vahidi, Siavash, Zev A. Ripstein, Jordan B. Juravsky, Enrico Rennella, Alfred L. Goldberg, Anthony K. Mittermaier, John L. Rubinstein, and Lewis E. Kay. "An allosteric switch regulatesMycobacterium tuberculosisClpP1P2 protease function as established by cryo-EM and methyl-TROSY NMR." Proceedings of the National Academy of Sciences 117, no. 11 (March 2, 2020): 5895–906. http://dx.doi.org/10.1073/pnas.1921630117.

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The 300-kDa ClpP1P2 protease fromMycobacterium tuberculosiscollaborates with the AAA+ (ATPases associated with a variety of cellular activities) unfoldases, ClpC1 and ClpX, to degrade substrate proteins. Unlike in other bacteria, all of the components of the Clp system are essential for growth and virulence of mycobacteria, and their inhibitors show promise as antibiotics. MtClpP1P2 is unique in that it contains a pair of distinct ClpP1 and ClpP2 rings and also requires the presence of activator peptides, such as benzoyl-leucyl-leucine (Bz-LL), for function. Understanding the structural basis for this requirement has been elusive but is critical for the rational design and improvement of antituberculosis (anti-TB) therapeutics that target the Clp system. Here, we present a combined biophysical and biochemical study to explore the structure–dynamics–function relationship in MtClpP1P2. Electron cryomicroscopy (cryo-EM) structures of apo and acyldepsipeptide-bound MtClpP1P2 explain their lack of activity by showing loss of a key β-sheet in a sequence known as the handle region that is critical for the proper formation of the catalytic triad. Methyl transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM, and biochemical assays show that, on binding Bz-LL or covalent inhibitors, MtClpP1P2 undergoes a conformational change from an inactive compact state to an active extended structure that can be explained by a modified Monod–Wyman–Changeux model. Our study establishes a critical role for the handle region as an on/off switch for function and shows extensive allosteric interactions involving both intra- and interring communication that regulate MtClpP1P2 activity and that can potentially be exploited by small molecules to targetM. tuberculosis.

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Wolff, Martin, Klaus Gast, Andreas Evers, Michael Kurz, Stefania Pfeiffer-Marek, Anja Schüler, Robert Seckler, and Anja Thalhammer. "A Conserved Hydrophobic Moiety and Helix–Helix Interactions Drive the Self-Assembly of the Incretin Analog Exendin-4." Biomolecules 11, no. 9 (September 3, 2021): 1305. http://dx.doi.org/10.3390/biom11091305.

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Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.

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Nagy, Tamás Milán, Krisztina Knapp, Eszter Illyés, István Timári, Gitta Schlosser, Gabriella Csík, Attila Borics, Zsuzsa Majer, and Katalin E. Kövér. "Photochemical and Structural Studies on Cyclic Peptide Models." Molecules 23, no. 9 (August 30, 2018): 2196. http://dx.doi.org/10.3390/molecules23092196.

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Ultra-violet (UV) irradiation has a significant impact on the structure and function of proteins that is supposed to be in relationship with the tryptophan-mediated photolysis of disulfide bonds. To investigate the correlation between the photoexcitation of Trp residues in polypeptides and the associated reduction of disulfide bridges, a series of small, cyclic oligopeptide models were analyzed in this work. Average distances between the aromatic side chains and the disulfide bridge were determined following molecular mechanics (MM) geometry optimizations. In this way, the possibility of cation–π interactions was also investigated. Molecular mechanics calculations revealed that the shortest distance between the side chain of the Trp residues and the disulfide bridge is approximately 5 Å in the cyclic pentapeptide models. Based on this, three tryptophan-containing cyclopeptide models were synthesized and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Experimental data and detailed molecular dynamics (MD) simulations were in good agreement with MM geometry calculations. Selected model peptides were subjected to photolytic degradation to study the correlation of structural features and the photolytic cleavage of disulfide bonds in solution. Formation of free sulfhydryl groups upon illumination with near UV light was monitored by fluorescence spectroscopy after chemical derivatization with 7-diethylamino-3-(4-maleimidophenyl)-4-methylcoumarin (CPM) and mass spectrometry. Liquid cromatography-mass spectrometry (LC-MS) measurements indicated the presence of multiple photooxidation products (e.g., dimers, multimers and other oxidated products), suggesting that besides the photolysis of disulfide bonds secondary photolytic processes take place.

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Clemente, Joyce S., Edward G. Gregorich, André J. Simpson, Rajeev Kumar, Denis Courtier-Murias, and Myrna J. Simpson. "Comparison of nuclear magnetic resonance methods for the analysis of organic matter composition from soil density and particle fractions." Environmental Chemistry 9, no. 1 (2012): 97. http://dx.doi.org/10.1071/en11096.

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Environmental contextThe association of specific organic matter (OM) compounds with clay mineral surfaces is believed to protect these compounds from degradation and thus result in long-term protection in soil. The molecular-level composition of soil OM associated with soil fractions was measured and compared using solid-state 13C nuclear magnetic resonance (NMR) and solution-state 1H NMR methods. Combining these methods allowed more detailed characterisation of OM associated with different soil fractions and will improve the understanding of OM dynamics in soil. AbstractOrganic matter (OM) associated with fine soil fractions is hypothesised to be protected from complete biodegradation by soil microbes. It is therefore important to understand the structure and stage of decomposition of OM associated with various soil fractions. Solid-state 13C nuclear magnetic resonance (NMR) spectroscopy has been used extensively to investigate the OM composition of soils and soil fractions. Solution-state 1H NMR spectroscopy has not been used as much but is an emerging tool for analysing soil OM because 1H NMR spectra are often better resolved and provide information that complements the structural information obtained from solid-state 13C NMR experiments. This study compares one-dimensional solution-state 1H NMR and solid-state 13C NMR methods for assessing the degradation and composition of OM in three different soils, and their light and clay-size fractions. The alkyl/O-alkyl degradation parameter was consistent across all NMR methods and showed that OM associated with clay-size fractions were at more advanced stages of degradation as compared to that in light density soil fractions. Solution-state 1H and diffusion edited (DE) 1H NMR results showed the presence of high concentrations of microbial-derived peptidoglycan and peptide side-chains in clay-sized fractions. Lignin was also identified in clay-sized fractions using solid-state 13C and solution-state 1H NMR techniques. The combination of solid-state 13C and solution-state 1H NMR methods provides a more detailed analysis of OM composition and thereby facilitates a better understanding of the fate and preservation of OM in soil.

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Penk, Anja, Matthias Müller, Holger A. Scheidt, Dieter Langosch, and Daniel Huster. "Structure and dynamics of the lipid modifications of a transmembrane α-helical peptide determined by 2H solid-state NMR spectroscopy." Biochimica et Biophysica Acta (BBA) - Biomembranes 1808, no. 3 (March 2011): 784–91. http://dx.doi.org/10.1016/j.bbamem.2010.12.015.

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Henriques, Sónia Troeira, Evelyne Deplazes, Nicole Lawrence, Olivier Cheneval, Stephanie Chaousis, Marco Inserra, Panumart Thongyoo, et al. "Interaction of Tarantula Venom Peptide ProTx-II with Lipid Membranes Is a Prerequisite for Its Inhibition of Human Voltage-gated Sodium Channel NaV1.7." Journal of Biological Chemistry 291, no. 33 (June 16, 2016): 17049–65. http://dx.doi.org/10.1074/jbc.m116.729095.

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ProTx-II is a disulfide-rich peptide toxin from tarantula venom able to inhibit the human voltage-gated sodium channel 1.7 (hNaV1.7), a channel reported to be involved in nociception, and thus it might have potential as a pain therapeutic. ProTx-II acts by binding to the membrane-embedded voltage sensor domain of hNaV1.7, but the precise peptide channel-binding site and the importance of membrane binding on the inhibitory activity of ProTx-II remain unknown. In this study, we examined the structure and membrane-binding properties of ProTx-II and several analogues using NMR spectroscopy, surface plasmon resonance, fluorescence spectroscopy, and molecular dynamics simulations. Our results show a direct correlation between ProTx-II membrane binding affinity and its potency as an hNaV1.7 channel inhibitor. The data support a model whereby a hydrophobic patch on the ProTx-II surface anchors the molecule at the cell surface in a position that optimizes interaction of the peptide with the binding site on the voltage sensor domain. This is the first study to demonstrate that binding of ProTx-II to the lipid membrane is directly linked to its potency as an hNaV1.7 channel inhibitor.

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van Well, Renate M., Luciana Marinelli, Cornelis Altona, Kees Erkelens, Gregg Siegal, Mark van Raaij, Antonio L. Llamas-Saiz, et al. "Conformational Analysis of Furanoid ε-Sugar Amino Acid Containing Cyclic Peptides by NMR Spectroscopy, Molecular Dynamics Simulation, and X-ray Crystallography: Evidence for a Novel Turn Structure." Journal of the American Chemical Society 125, no. 36 (September 2003): 10822–29. http://dx.doi.org/10.1021/ja035461+.

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Arvidsson, Klas, J�ri Jarvet, Peter Allard, and Anders Ehrenberg. "Solution structure by 1H and dynamics by natural abundance 13C NMR of a receptor recognising peptide derived from a C-terminal fragment of neuropeptide Y." Journal of Biomolecular NMR 4, no. 5 (September 1994): 653–72. http://dx.doi.org/10.1007/bf00404276.

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Meredith, Jeffrey J., Antoine Dufour, and Martha D. Bruch. "Comparison of the Structure and Dynamics of the Antibiotic Peptide Polymyxin B and the Inactive Nonapeptide in Aqueous Trifluoroethanol by NMR Spectroscopy." Journal of Physical Chemistry B 113, no. 2 (January 15, 2009): 544–51. http://dx.doi.org/10.1021/jp808379x.

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Yee, Adelinda A., and Joe D. J. O'Neil. "Uniform nitrogen-15 labeling of a fungal peptide: The structure and dynamics of an alamethicin by nitrogen-15 and proton NMR spectroscopy." Biochemistry 31, no. 12 (March 1992): 3135–43. http://dx.doi.org/10.1021/bi00127a014.

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Kokubu, Ryoka, Shiho Ohno, Hirohide Kuratani, Yuka Takahashi, Noriyoshi Manabe, Hiroki Shimizu, Yasunori Chiba, et al. "O-Glycan-Dependent Interaction between MUC1 Glycopeptide and MY.1E12 Antibody by NMR, Molecular Dynamics and Docking Simulations." International Journal of Molecular Sciences 23, no. 14 (July 16, 2022): 7855. http://dx.doi.org/10.3390/ijms23147855.

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Anti-mucin1 (MUC1) antibodies have been widely used for breast cancer diagnosis and treatment. This is based on the fact that MUC1 undergoes aberrant glycosylation upon cancer progression, and anti-MUC1 antibodies differentiate changes in glycan structure. MY.1E12 is a promising anti-MUC1 antibody with a distinct specificity toward MUC1 modified with an immature O-glycan (NeuAcα(2-3)Galβ(1-3)GalNAc) on a specific Thr. However, the structural basis for the interaction between MY.1E12 and MUC1 remains unclear. The aim of this study is to elucidate the mode of interaction between MY.1E12 and MUC1 O-glycopeptide by NMR, molecular dynamics (MD) and docking simulations. NMR titration using MUC1 O-glycopeptides suggests that the epitope is located within the O-linked glycan and near the O-glycosylation site. MD simulations of MUC1 glycopeptide showed that the O-glycosylation significantly limits the flexibility of the peptide backbone and side chain of the O-glycosylated Thr. Docking simulations using modeled MY.1E12 Fv and MUC1 O-glycopeptide, suggest that VH mainly contributes to the recognition of the MUC1 peptide portion while VL mainly binds to the O-glycan part. The VH/VL-shared recognition mode of this antibody may be used as a template for the rational design and development of anti-glycopeptide antibodies.

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Charretier, E., and M. Guéron. "Application de la résonance magnétique nucléaire à la détermination de la structure des protéines en solution." Biochemistry and Cell Biology 69, no. 5-6 (May 1, 1991): 322–35. http://dx.doi.org/10.1139/o91-051.

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Knowledge of three-dimensional structure is a key factor in protein engineering. It is useful, for example, in predicting and understanding the functional consequences of specific substitution of one or more amino acids of the polypeptide chain. It is also necessary for the design of new effectors or analogs of the substrates of enzymes and receptors. X-ray diffraction by crystals of the biomolecule was for a long time the only method of determining three-dimensional structures. In the last 5 years, it has been joined by a new technique, two-dimensional nuclear magnetic resonance (2D NMR), which can resolve the structure of middle-sized proteins ( < 10 kilodaltons). The technique is applied on solutions whose pH, ionic strength, and temperature can be chosen and changed. The two basic measurements, COSY and NOESY, detect respectively the systems of hydrogen nuclei, or protons, coupled through covalent bonds, and those in which the interproton distances are less than 0.5 nm. A systematic strategy leads from resonance assignments of the two-dimensional spectrum to molecular modeling with constraints and finally to the determination of the molecular structure in the solution. Much sophistication is needed even today for the first task, the assignment of the resonances. Each of the COSY and NOESY spectra is a two-dimensional map, where the diagonal line is the one-dimensional spectrum, and the off-diagonal peaks indicate connectivities between protons. Peak assignment to a specific type of amino acid is based on the pattern of scalar couplings observed in the COSY spectrum. Next, the amino acids are positioned in the primary sequence, using the spatial proximities of polypeptide chain protons, as observed in the NOESY spectrum. The principal secondary structures (α helix, β sheets, etc.) are then identified by their specific connectivities. The tertiary structure is detected by NOESY connectivities between protons of different amino acids which are far apart in the primary sequence. The distance constraints from the NOESY connectivities also provide the starting point for modeling the tertiary structure. This is then refined using distance geometry and molecular dynamics algorithms. The resolution of the structures obtained with the help of recent algorithmic developments may be comparable to that provided by X-ray diffraction. The COSY measurement can be completed or substituted by other measurements, useful albeit more complex. For example, the HOHAHA experiment, currently in wide use, gives the correlations through multiple covalent bonds. Multiquanta experiments, which select systems of a given number of coupled spins, provide spectral simplification. To help with the sequential assignment, which remains a limiting step, one may substitute amino acids isotopically labeled with 15N or 13C. Nuclear magnetic resonance of these nuclei is detected either directly or by heteronuclear proton NMR. In the latter case, heteronuclear cross-peaks indicate connectivities between protons and the isotopic nuclei, 1SN and 13C. This labeling is very useful for proteins with more than 100 amino acids and for proteins exhibiting low-resolution spectra. Resolution can also be enhanced by the combination of two-dimensional experiments, giving rise to 3D NMR. The graphic representation of a three-dimensional experiment is a cube whose sections correspond to virtual two-dimensional measurements. The 3D NMR can be homonuclear or, in the case of isotopically substituted proteins, heteronuclear. The time for a single experiment reaches several days. The memory needed for data acquisition and processing is greater than for two-dimensional experiments. Large parts of the data processing, such as peak detection or the recognition of secondary structure connectivities can be automated. Two-dimensional NMR is becoming a routine technique for peptide and protein structure determination in the laboratories of the pharmaceutical firms.Key words: protein engineering, three-dimensional structure, nuclear magnetic resonance, correlated spectroscopy, nuclear Overhauser effect spectroscopy.

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Bereiter, Raphael, Maximilian Himmelstoß, Eva Renard, Elisabeth Mairhofer, Michaela Egger, Kathrin Breuker, Christoph Kreutz, Eric Ennifar, and Ronald Micura. "Impact of 3-deazapurine nucleobases on RNA properties." Nucleic Acids Research 49, no. 8 (April 15, 2021): 4281–93. http://dx.doi.org/10.1093/nar/gkab256.

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Abstract Deazapurine nucleosides such as 3-deazaadenosine (c3A) are crucial for atomic mutagenesis studies of functional RNAs. They were the key for our current mechanistic understanding of ribosomal peptide bond formation and of phosphodiester cleavage in recently discovered small ribozymes, such as twister and pistol RNAs. Here, we present a comprehensive study on the impact of c3A and the thus far underinvestigated 3-deazaguanosine (c3G) on RNA properties. We found that these nucleosides can decrease thermodynamic stability of base pairing to a significant extent. The effects are much more pronounced for 3-deazapurine nucleosides compared to their constitutional isomers of 7-deazapurine nucleosides (c7G, c7A). We furthermore investigated base pair opening dynamics by solution NMR spectroscopy and revealed significantly enhanced imino proton exchange rates. Additionally, we solved the X-ray structure of a c3A-modified RNA and visualized the hydration pattern of the minor groove. Importantly, the characteristic water molecule that is hydrogen-bonded to the purine N3 atom and always observed in a natural double helix is lacking in the 3-deazapurine-modified counterpart. Both, the findings by NMR and X-ray crystallographic methods hence provide a rationale for the reduced pairing strength. Taken together, our comparative study is a first major step towards a comprehensive understanding of this important class of nucleoside modifications.

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Deshmukh, Lalit, Rodolfo Ghirlando, and G. Marius Clore. "Investigation of the Structure and Dynamics of the Capsid-Spacer Peptide 1-Nucleocapsid Fragment of the HIV-1 Gag Polyprotein by Solution NMR Spectroscopy." Angewandte Chemie 126, no. 4 (December 11, 2013): 1043–46. http://dx.doi.org/10.1002/ange.201309127.

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Deshmukh, Lalit, Rodolfo Ghirlando, and G. Marius Clore. "Investigation of the Structure and Dynamics of the Capsid-Spacer Peptide 1-Nucleocapsid Fragment of the HIV-1 Gag Polyprotein by Solution NMR Spectroscopy." Angewandte Chemie International Edition 53, no. 4 (December 11, 2013): 1025–28. http://dx.doi.org/10.1002/anie.201309127.

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Sgourakis, Nikolaos, Andrew C. McShan, Kannan Natarajan, Vlad K. Kumirov, David Flores-Solis, Jiansheng Jiang, Mareike Badstuebner, Evgenii L. Kovrigin, and David H. Margulies. "Chaperone-assisted peptide exchange on MHC-I is driven by a negative allostery release cycle: Implications for a role of peptide-editing Molecular Chaperones in scrutinizing the peptide repertoire." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 99.23. http://dx.doi.org/10.4049/jimmunol.200.supp.99.23.

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Abstract Molecular chaperones TAPBPR (TAP-binding protein related) and tapasin associate with major histocompatibility complex class I (MHC-I) to promote the loading of antigenic peptides through a poorly understood mechanism. Here, we use solution Nuclear Magnetic Resonance (NMR) spectroscopy to probe TAPBPR-induced changes on MHC-I. Dynamic motions present in the empty MHC groove become progressively dampened with increasing peptide occupancy, while allosteric communication between the A- and F-pockets regulates a conformational switch located near the TAPBPR binding site, which is crucial for chaperone release from the complex. Our analysis of NMR data recorded for a range of TAPBPR complexes prepared with both murine H2 and human HLA alleles complements the recent X-ray structures to provide atomic-resolution mechanistic insights into the selection of optimal peptide sequences for the displayed antigen repertoire. In particular, our results show that negative allosteric coupling between the MHC groove and chaperone binding sites allows TAPBPR to proofread MHC molecules containing a range of different peptides. Since the affinity of incoming peptides for the empty groove is greatly reduced in the chaperone complex, (micromolar range, relative to nanomolar for the free MHC), these interactions can provide a mechanism for optimizing the peptide repertoire, where only the highest-affinity peptides can drive chaperone release. Finally, our results suggest that TAPBPR may promote the dissociation of tightly bound peptides from MHC molecules, thereby further scrutinizing the displayed repertoire. These findings imply a similar mechanism for the specificity and editing function of tapasin in the peptide-loading complex.

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Wang, Jun, Atsushi Tsutsumi, Kiyonobu Yokota, Izuru Kawamura, and Akira Naito. "2A1412 Dynamic structure of antimicrobial peptide alamethicin bound to the acidic lipid bilayers as revealed by solid-state NMR spectroscopy(Biol & Artifi memb 2: Structure & Property, Dynamics, Signal transduction,The 48th Annual Meeting of the Biophysical Society of Japan)." Seibutsu Butsuri 51, supplement (2011): S73. http://dx.doi.org/10.2142/biophys.51.s73_1.

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Deshmukh, Lalit, Rodolfo Ghirlando, and G. Marius Clore. "Conformation and dynamics of the Gag polyprotein of the human immunodeficiency virus 1 studied by NMR spectroscopy." Proceedings of the National Academy of Sciences 112, no. 11 (February 23, 2015): 3374–79. http://dx.doi.org/10.1073/pnas.1501985112.

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Assembly and maturation of the human immunodeficiency virus type 1 (HIV-1) are governed by the Gag polyprotein. Here we study the conformation and dynamics of a large HIV-1 Gag fragment comprising the matrix, capsid, spacer peptide 1 and nucleocapsid domains (referred to as ΔGag) by heteronuclear multidimensional NMR spectroscopy. In solution, ΔGag exists in a dynamic equilibrium between monomeric and dimeric states. In the presence of nucleic acids and at low ionic strength ΔGag assembles into immature virus-like particles. The structured domains of ΔGag (matrix, the N- and C-terminal domains of capsid, and the N- and C-terminal zinc knuckles of nucleocapsid) retain their fold and reorient semi-independently of one another; the linkers connecting the structural domains, including spacer peptide 1 that connects capsid to nucleocapsid, are intrinsically disordered. Structural changes in ΔGag upon proteolytic processing by HIV-1 protease, monitored by NMR in real-time, demonstrate that the conformational transition of the N-terminal 13 residues of capsid from an intrinsically disordered coil to a β-hairpin upon cleavage at the matrix|capsid junction occurs five times faster than cleavage at the capsid|spacer peptide 1 junction. Finally, nucleic acids interact with both nucleocapsid and matrix domains, and proteolytic processing at the spacer peptide 1|nucleocapsid junction by HIV-1 protease is accelerated in the presence of single-stranded DNA.

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Journal articles on the topic 'Structure and Dynamics of Peptides by NMR Spectroscopy'

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