Journal articles on the topic 'Ligards (Biochemistry)'
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1
Mitchell, Peter D. "Foundations of Vectorial Metabolism and Osmochemistry." Bioscience Reports 24, no. 4-5 (August 10, 2004): 386–435. http://dx.doi.org/10.1007/s10540-005-2739-2.
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Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.
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Mitchell, Peter. "Foundations of vectorial metabolism and osmochemistry." Bioscience Reports 11, no. 6 (December 1, 1991): 297–346. http://dx.doi.org/10.1007/bf01130212.
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Chemical transformations, like osmotic translocations, are transport processes when looked at in detail. In chemiosmotic systems, the pathways of specific ligand conduction are spatially orientated through osmoenzymes and porters in which the actions of chemical group, electron and solute transfer occur as vectorial (or higher tensorial order) diffusion processes down gradients of total potential energy that represent real spatially-directed fields of force. Thus, it has been possible to describe classical bag-of-enzymes biochemistry as well as membrane biochemistry in terms of transport. But it would not have been possible to explain biological transport in terms of classical transformational biochemistry or chemistry. The recognition of this conceptual asymmetry in favour of transport has seemed to be upsetting to some biochemists and chemists; and they have resisted the shift towards thinking primarily in terms of the vectorial forces and co-linear displacements of ligands in place of their much less informative scalar products that correspond to the conventional scalar energies. Nevertheless, considerable progress has been made in establishing vectorial metabolism and osmochemistry as acceptable biochemical disciplines embracing transport and metabolism, and bioenergetics has been fundamentally transformed as a result.
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Chin, G. J. "BIOCHEMISTRY: Making Metal Ligands." Science 298, no. 5597 (November 15, 2002): 1303b—1303. http://dx.doi.org/10.1126/science.298.5597.1303b.
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Velesinović, Aleksandar, and Goran Nikolić. "Protein-protein interaction networks and protein-ligand docking: Contemporary insights and future perspectives." Acta Facultatis Medicae Naissensis 38, no. 1 (2021): 5–17. http://dx.doi.org/10.5937/afmnai38-28322.
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Traditional research means, such as in vitro and in vivo models, have consistently been used by scientists to test hypotheses in biochemistry. Computational (in silico) methods have been increasingly devised and applied to testing and hypothesis development in biochemistry over the last decade. The aim of in silico methods is to analyze the quantitative aspects of scientific (big) data, whether these are stored in databases for large data or generated with the use of sophisticated modeling and simulation tools; to gain a fundamental understanding of numerous biochemical processes related, in particular, to large biological macromolecules by applying computational means to big biological data sets, and by computing biological system behavior. Computational methods used in biochemistry studies include proteomics-based bioinformatics, genome-wide mapping of protein-DNA interaction, as well as high-throughput mapping of the protein-protein interaction networks. Some of the vastly used molecular modeling and simulation techniques are Monte Carlo and Langevin (stochastic, Brownian) dynamics, statistical thermodynamics, molecular dynamics, continuum electrostatics, protein-ligand docking, protein-ligand affinity calculations, protein modeling techniques, and the protein folding process and enzyme action computer simulation. This paper presents a short review of two important methods used in the studies of biochemistry - protein-ligand docking and the prediction of protein-protein interaction networks.
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Di Marzo, Vincenzo, and Dale G. Deutsch. "Biochemistry of the Endogenous Ligands of Cannabinoid Receptors." Neurobiology of Disease 5, no. 6 (December 1998): 386–404. http://dx.doi.org/10.1006/nbdi.1998.0214.
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Cheloha, Ross W., Thibault J. Harmand, Charlotte Wijne, Thomas U. Schwartz, and Hidde L. Ploegh. "Exploring cellular biochemistry with nanobodies." Journal of Biological Chemistry 295, no. 45 (August 31, 2020): 15307–27. http://dx.doi.org/10.1074/jbc.rev120.012960.
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Reagents that bind tightly and specifically to biomolecules of interest remain essential in the exploration of biology and in their ultimate application to medicine. Besides ligands for receptors of known specificity, agents commonly used for this purpose are monoclonal antibodies derived from mice, rabbits, and other animals. However, such antibodies can be expensive to produce, challenging to engineer, and are not necessarily stable in the context of the cellular cytoplasm, a reducing environment. Heavy chain–only antibodies, discovered in camelids, have been truncated to yield single-domain antibody fragments (VHHs or nanobodies) that overcome many of these shortcomings. Whereas they are known as crystallization chaperones for membrane proteins or as simple alternatives to conventional antibodies, nanobodies have been applied in settings where the use of standard antibodies or their derivatives would be impractical or impossible. We review recent examples in which the unique properties of nanobodies have been combined with complementary methods, such as chemical functionalization, to provide tools with unique and useful properties.
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Hutchens, T. W., and J. O. Porath. "Protein recognition of immobilized ligands: promotion of selective adsorption." Clinical Chemistry 33, no. 9 (September 1, 1987): 1502–8. http://dx.doi.org/10.1093/clinchem/33.9.1502.
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Abstract We are using simple immobilized ligands to evaluate the biochemistry and mechanisms of selective, high-affinity, protein adsorption events. Several specific means have recently been developed to more selectively utilize the favorable entropy changes associated with the displacement of protein-bound water during the formation and stabilization of protein-ligand recognition events. For protein and peptide immobilization these include, besides hydrophobic interaction, for example, metal ion, pi-electron-mediated, and thiophilic interactions. This latter type of protein-ligand recognition process represents a previously unrecognized interaction mechanism of considerable selectivity, affinity, and utility. Specific examples of the above-mentioned principles and protein fractionations include (a) thiophilic adsorption of immunoglobulins to achieve immunoglobulin-free serum for in vitro production and purification of monoclonal antibodies and (b) urea-induced binding of estrogen-receptor proteins to immobilized DNA. The interaction mechanisms are discussed in terms of the molecular architecture of protein surfaces. We present possibilities for the further utilization of these immobilized ligands and their associated proteins in the areas of clinical biochemistry and immunology.
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Seasholtz, AF, RA Valverde, and RJ Denver. "Corticotropin-releasing hormone-binding protein: biochemistry and function from fishes to mammals." Journal of Endocrinology 175, no. 1 (October 1, 2002): 89–97. http://dx.doi.org/10.1677/joe.0.1750089.
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Corticotropin-releasing hormone (CRH) plays multiple roles in vertebrate species. In mammals, it is the major hypothalamic releasing factor for pituitary adrenocorticotropin secretion, and is a neurotransmitter or neuromodulator at other sites in the central nervous system. In non-mammalian vertebrates, CRH not only acts as a neurotransmitter and hypophysiotropin, it also acts as a potent thyrotropin-releasing factor, allowing CRH to regulate both the adrenal and thyroid axes, especially in development. The recent discovery of a family of CRH-like peptides suggests that multiple CRH-like ligands may play important roles in these functions. The biological effects of CRH and the other CRH-like ligands are mediated and modulated not only by CRH receptors, but also via a highly conserved CRH-binding protein (CRH-BP). The CRH-BP has been identified not only in mammals, but also in non-mammalian vertebrates including fishes, amphibians, and birds, suggesting that it is a phylogenetically ancient protein with extensive structural and functional conservation. In this review, we discuss the biochemical properties of the characterized CRH-BPs and the functional roles of the CRH-BP. While much of the in vitro and in vivo data to date support an 'inhibitory' role for the CRH-BP in which it binds CRH and other CRH-like ligands and prevents the activation of CRH receptors, the possibility that the CRH-BP may also exhibit diverse extra- and intracellular roles in a cell-specific fashion and at specific times in development is also discussed.
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Caflisch, Amedeo, Rudolf Wälchli, and Claus Ehrhardt. "Computer-Aided Design of Thrombin Inhibitors." Physiology 13, no. 4 (August 1998): 182–89. http://dx.doi.org/10.1152/physiologyonline.1998.13.4.182.
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Computer-aided ligand design is an active, challenging, and multidisciplinary research field that blends knowledge of biochemistry, physics, and computer sciences. Whenever it is possible to experimentally determine or to model the three-dimensional structure of a pharmacologically relevant enzyme or receptor, computational approaches can be used to design specific high-affinity ligands. This article describes methods, applications, and perspectives of computer-assisted ligand design.
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Sharon, Nathan. "Protein–carbohydrate interactions: At the heart of biochemistry." Biochemist 28, no. 3 (June 1, 2006): 13–17. http://dx.doi.org/10.1042/bio02803013.
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Proteins that possess the ability to bind carbohydrates specifically and reversibly abound in nature, being present in all living organisms, from viruses to humans. Their interactions with their ligands are the basis of a myriad of biological processes, both normal and pathological1–3 (Table 1). The high selectivity required for these interactions is provided by a specific stereochemical fit between complementary molecules, the protein on the one hand and the carbohydrate on the other. This concept has its origins in the lock-and-key hypothesis, introduced by Emil Fischer at the end of the 19th Century to explain the specificity of interactions between enzymes (he studied glycosidases) and their substrates (carbohydrates), i.e. between molecules in solution. In time it was extended to describe the interactions of cells with soluble molecules and with other cells.
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Vanin, Anatoly F. "Dinitrosyl iron complexes with thiolate ligands: Physico-chemistry, biochemistry and physiology." Nitric Oxide 21, no. 1 (August 2009): 1–13. http://dx.doi.org/10.1016/j.niox.2009.03.005.
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Isab, Anvarhusein A., and Saeed Ahmad. "Applications of NMR spectroscopy in understanding the gold biochemistry." Spectroscopy 20, no. 3 (2006): 109–23. http://dx.doi.org/10.1155/2006/314052.
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Gold-based drugs have been successfully used for the treatment of rheumatoid arthritis. When administered, they undergo ligand exchange reactions in the body with biofluids, cells and proteins. NMR spectroscopy is a very useful technique for probing these ligand exchange reactions under physiological conditions. The strength of the binding ligands can be estimated by studying the chemical shift changes in13C and31P NMR. It is also a powerful method for investigating the kinetics and thermodynamics of the exchange reactions of gold drugs with biomolecules. The purpose of this review report is to highlight the importance of NMR spectroscopy in the study of gold biochemistry and to bridge the fairly large gap in the progress of this interesting area of bioinorganic chemistry.
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Weller, Malcolm P. I. "Workshop on Schizophrenia." Bulletin of the Royal College of Psychiatrists 10, no. 10 (October 1986): 277. http://dx.doi.org/10.1192/s0140078900023099.
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Representatives from 19 countries met by invitation to discuss their most recent research findings at the Third Biannual Workshop on Schizophrenia, Schladming, Austria 26–31 January 1986, organised by Dr T. J. Crow (MRC, Northwick Park Hospital) and Professor S. R. Hirsch (Charing Cross Hospital Medical School). The thrust was highly biological with biochemistry and brain structure much in the fore, assisted by much greater resolution of imageing techniques and the development of specific ligands for synaptic receptors.
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Herrera, Raul, and M. A. Moya-León. "Symposium 20 - PABMB: Teaching biochemistry in a connected world: KEEPING 3D RESOURCES IN THE WEB TO LEARN ON PROTEIN STRUCTURE." Revista de Ensino de Bioquímica 13 (August 24, 2015): 41. http://dx.doi.org/10.16923/reb.v13i2.609.
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Symposium 20 - PABMB: Teaching biochemistry in a connected world Chair: Miguel Castanho, Universidade de Lisboa, PortugalAbstract:The new paradigm of higher education requires new teaching strategies to meet the learning objectives of biochemistry courses. Teaching biochemistry in the current state of science and society requires a special motivation for learning, especially for students of degrees other than Biochemistry. The traditional way of teaching, based on the teacher-student relationship, mostly unidirectional, does not fulfil the needs imposed in this era. Considering the current situation universities students require new abilities in their training and the use of computers can constitute a place for discovery and research, enabling the experience of new and diverse situations. The design of teaching material for undergraduate students who take biochemistry courses as complementary subject on their careers should be seen as an opportunity to complement theoretical aspects on the current courses. Three different approaches could be used: (I) a description of the basic concepts, like in a book but using dynamics figures. (II) Modelling proteins highlighting key motifs at the three-dimensional structure and residues where inhibitors can be attached. And (III) elaborating active quizzes where students can be driven on their learning. Building knowledge based on practical experience can improve student competences on basic science and the learning process can be complemented in the use of dynamics models. On the other hand, exploring protein structures from the web could give students a better comprehension of residues interaction and non-covalent forces involved in protein-protein or protein-ligand interaction. The use of dynamic models improves the comprehension of protein structure and their special link to amino acids residues or ligands. This work was supported by Anillo ACT1110 project. Key Words: protein structure, 3D source, learning activities.
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Bezerra, Eveline M., Érika C. de Alvarenga, Ricardo P. dos Santos, Jeanlex S. de Sousa, Umberto L. Fulco, Valder N. Freire, Eudenilson L. Albuquerque, and Roner F. da Costa. "Losartan as an ACE inhibitor: a description of the mechanism of action through quantum biochemistry." RSC Advances 12, no. 44 (2022): 28395–404. http://dx.doi.org/10.1039/d2ra04340h.
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Projection of the interaction energy with ligands lisinopril (LPR) and losartan (LST) for each amino acid of the somatic angiotensin converting enzyme (sACE) mapped onto the molecular surface, according to the scale bar.
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Bovin, N. V., and H. J. Gabius. "Polymer-immobilized carbohydrate ligands: versatile chemical tools for biochemistry and medical sciences." Chemical Society Reviews 24, no. 6 (1995): 413. http://dx.doi.org/10.1039/cs9952400413.
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Lamazares, Emilio, Desmond MacLeod-Carey, Fernando P. Miranda, and Karel Mena-Ulecia. "Theoretical Evaluation of Novel Thermolysin Inhibitors from Bacillus thermoproteolyticus. Possible Antibacterial Agents." Molecules 26, no. 2 (January 13, 2021): 386. http://dx.doi.org/10.3390/molecules26020386.
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The search for new antibacterial agents that could decrease bacterial resistance is a subject in continuous development. Gram-negative and Gram-positive bacteria possess a group of metalloproteins belonging to the MEROPS peptidase (M4) family, which is the main virulence factor of these bacteria. In this work, we used the previous results of a computational biochemistry protocol of a series of ligands designed in silico using thermolysin as a model for the search of antihypertensive agents. Here, thermolysin from Bacillus thermoproteolyticus, a metalloprotein of the M4 family, was used to determine the most promising candidate as an antibacterial agent. Our results from docking, molecular dynamics simulation, molecular mechanics Poisson–Boltzmann (MM-PBSA) method, ligand efficiency, and ADME-Tox properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) indicate that the designed ligands were adequately oriented in the thermolysin active site. The Lig783, Lig2177, and Lig3444 compounds showed the best dynamic behavior; however, from the ADME-Tox calculated properties, Lig783 was selected as the unique antibacterial agent candidate amongst the designed ligands.
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Shamshad, Bushra, Rifat Ara Jamal, Uzma Ashiq, Mohammad Mahroof-Tahir, and Muhammad Saleem. "Cytotoxic, antiglycation and carbonic anhydrase inhibition studies of chromium(III)-aroylhydrazine complexes." European Journal of Chemistry 9, no. 3 (September 30, 2018): 168–77. http://dx.doi.org/10.5155/eurjchem.9.3.168-177.1735.
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In order to further reveal the chemistry and biochemistry of chromium(III) complexes, the present work illuminates the formation of chromium(III) complexes with aroylhydrazine ligands with their physical, chemical and spectral studies. Another significant contribution of this study is the evaluation of the cytotoxic activity, antiglycation property and carbonic anhydrase inhibition study of synthesized chromium(III)-aroylhydrazine complexes. Synthesis and structural investigation of aroylhydrazine ligands (1-7) and their chromium(III) complexes (1a-7a) were carried out by using elemental analysis (C, H, N), physical (conductivity measurements) and spectral (EI-Mass, ESI-Mass, FTIR and UV-Visible) methods. These physical, analytical and spectral data supports that all chromium(III)-aroylhydrazine complexes exhibit an octahedral geometry in which ligand exhibits as a bidentate coordination and two water molecules coordinated at equatorial positions with general formula [Cr(L)2(H2O)2]Cl3. Cytotoxic investigations shows that synthesized chromium(III)-aroylhydrazine complexes were not found to be toxic against normal cells so these compounds were further studied for other biological activities. Moreover, aroylhydrazine ligands and their chromium(III) complexes were examined for their antiglycation activity in which ligands were found inactive whereas chromium(III)-aroylhydrazine complexes showed significant inhibition of the process of protein glycation. Similarly, in carbonic anhydrase inhibition studies all aroylhydrazine ligands were observed inactive while some of chromium(III)-aroylhydrazine complexes showed potential in carbonic anhydrase inhibition.
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Rahier, A., P. Benveniste, T. Husselstein, and M. Taton. "Biochemistry and site-directed mutational analysis of Δ7-sterol-C5(6)-desaturase." Biochemical Society Transactions 28, no. 6 (December 1, 2000): 799–803. http://dx.doi.org/10.1042/bst0280799.
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This report describes recent work on the process of desaturation at C5(6) of sterol precursors in plants. Biochemical characterization of the plant Δ7-sterol C5(6)-desaturase (5-DES) indicates that the enzyme system involved shows important similarities to the soluble and membrane-bound non-haem iron desaturases found in eukaryotes, including cyanide and hydrophobic chelators sensitivity, CO resistance and a requirement for exogenous reductant and molecular oxygen. Site-directed mutational analysis of highly conserved residues in 5-DES indicated that eight histidine residues from three histidine-rich motifs were essential for the catalysis, possibly by providing the ligands for a putative Fe centre. This mutational analysis also revealed the catalytic role of the functionally conserved Thr-114.
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Anwar, Hira, Rosenani A. Haque, Rahman Shah Zaib Saleem, and Muhammad Adnan Iqbal. "Recent advances in synthesis of organometallic complexes of indium." Reviews in Inorganic Chemistry 40, no. 3 (September 25, 2020): 107–51. http://dx.doi.org/10.1515/revic-2020-0005.
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AbstractThe indium complexes are being used in many applications like catalysis, optoelectronics, sensors, solar cells, biochemistry, medicine, infrared (IR) mirrors and thin-film transistors (TFTs). In organometallic complexes of indium, it forms different types of complexes with single, double, triple and tetra linkages by coordinating with numerous elements like C, N, O and S and also with some other elements like Se and Ru. So, the present study comprises all the possible ways to synthesize the indium complexes by reacting with different organic ligands; most of them are N-heterocyclic carbenes, amines, amides and phenols. The commonly used solvents for these syntheses are tetrahydrofuran, dichloromethane, toluene, benzene, dimethyl sulfoxide (DMSO) and water. According to the nature of the ligands, indium complexes were reported at different temperatures and stirring time. Because of their unique characteristics, the organometallic chemistry of group 13 metal indium complexes remains a subject of continuing interest in synthetic chemistry as well as material science.
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Linton, Kenneth J. "Structure and Function of ABC Transporters." Physiology 22, no. 2 (April 2007): 122–30. http://dx.doi.org/10.1152/physiol.00046.2006.
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ATP binding cassette transporters are ubiquitous integral membrane proteins that actively transport ligands across biological membranes, a process critical for most aspects of cell physiology. These proteins are important clinically and economically. Their dysfunction underlies a number of human genetic diseases, and the ability of some to pump cytotoxic molecules from cells confers resistance to antibiotics, herbicides, and chemotherapeutic drugs. Recent structure analyses interpreted in light of a large body of biochemistry has resulted in the ATP-switch model for function in which the paired nucleotide binding domains switch between an ATP-dependent closed conformation and a nucleotide-free, open conformation to drive the translocation of ligand.
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Polokhina, K. V., D. E. Kytova, A. V. Shtemenko, and N. I. Shtemenko. "Cytotoxic activity of the cluster rhenium compound with ?-alanine ligands." Ukrainian Biochemical Journal 92, no. 1 (February 7, 2020): 120–26. http://dx.doi.org/10.15407/ubj92.01.120.
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Albuquerque, E. L., Ana Beatriz M. L. A. Tavares, L. R. da Silva, J. X. Lima-Neto, and U. L. Fulco. "A quantum biochemistry investigation of cancer immunotherapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e14558-e14558. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14558.
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e14558 Background: Immunotherapy is a procedure to boost the patient's own immune system to fight diseases such as cancer. In some types of cancer, it has been found that the programmed cell death receptor PD-1 impedes the body's immune defenses from functioning at full strength. Therefore drugs, like pembrolizumab, which prevent the interaction between this protein and the T-cells, may be a key tool to avoid the onset of cancer tumors. Methods: The aim of this work is to describe the interaction energies between the protein PD-1 and its drug inhibitor pembrolizumab by using a quantum biochemistry calculations, taking advantage of the X-ray crystal structure of the protein PD-1 in complex with its inhibitor. The protonation state of the drug was obtained using the Marvin Sketch code (Marvin Beans Suite). The optimization procedure was performed using the parametrization tool for organic molecules CHARMM (Chemistry at Harvard Macromolecular Mechanics). Afterwards, simulations within the density functional theory (DFT) framework were carried out by using the Gaussian code to provide a detailed energy profile of the interactions between the inhibitor and the receptor. Results: The interaction energy between each PD-1 molecule and the drug was calculated considering any significant attractive and repulsive drug’s amino acid residues. A searchfor an optimal binding pocket radius was done, looking for no significantvariation in the total binding energy. The converged binding pocket radius was found to be 1.5 nm, comprising a total of 145 amino acids residues displayed in a BIRD (Binding site, Interaction energy and Residues Domain) graphic panel. Although it was observed few repulsive interactions, the attractive ones were predominant, pointing out to a strong inhibition of the programmed cell death receptor. Conclusions: Immunotherapy is ranked nowadays as an important alternative to treat cancer. Among the drugs been tested, those blocking the protein PD-1 and its ligands have been considered an efficient way to trigger the T-cells. In this context, the computational method used in this work is a low cost efficient first step to unveil the drug’s amino-acids residues that play the most important role on the binding affinity of the receptor-ligand complex.
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LENFERINK, Anne E. G., Albert D. G. De ROOS, Marianne J. H. Van VUGT, Monique L. M. Van De POLL, and Everardus J. J. Van ZOELEN. "The linear C-terminal regions of epidermal growth factor (EGF) and transforming growth factor-α bind to different epitopes on the human EGF receptor." Biochemical Journal 336, no. 1 (November 15, 1998): 147–51. http://dx.doi.org/10.1042/bj3360147.
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Epidermal growth factor (EGF) and transforming growth factor-α (TGFα) bind with similar affinities in a competitive fashion to the human EGF receptor, and basically induce similar mitogenic responses. In spite of the fact that EGF and TGFα are structurally alike, it is still not clear if the two growth factors bind the receptor in an identical manner. The observation that the 13A9 antibody blocks binding of TGFα, but not that of EGF, to the human EGF receptor [Winkler, O'Connor, Winget and Fendly (1989) Biochemistry 28, 6373–6378] suggests that their binding characteristics are not identical. In the present study we have made use of a set of EGF/TGFα chimaeric molecules to show that the 13A9 antibody blocks receptor binding of ligands with TGFα sequences, but not of ligands with EGF sequences, in their C-terminal linear regions. Using HaCaT human keratinocyte cells in culture, it was determined that ligands that are able to bind the EGF receptor in the presence of 13A9 are also able to induce calcium release from intracellular stores in these cells, indicating that these ligands have the ability to activate the EGF receptor in the presence of the antibody. From these data it is concluded that the flexible C-terminal linear domains of EGF and TGFα bind to separate sequences on the EGF receptor, such that the binding domain of TGFα, but not that of EGF, overlaps with the binding epitope of the 13A9 antibody.
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BOVIN, N. V., and H. J. GABIUS. "ChemInform Abstract: Polymer-Immobilized Carbohydrate Ligands: Versatile Chemical Tools for Biochemistry and Medical Sciences." ChemInform 27, no. 29 (August 5, 2010): no. http://dx.doi.org/10.1002/chin.199629305.
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Vidad, Ashley Ryan, Stephen Macaspac, and Ho Leung Ng. "Locating ligand binding sites in G-protein coupled receptors using combined information from docking and sequence conservation." PeerJ 9 (September 24, 2021): e12219. http://dx.doi.org/10.7717/peerj.12219.
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GPCRs (G-protein coupled receptors) are the largest family of drug targets and share a conserved structure. Binding sites are unknown for many important GPCR ligands due to the difficulties of GPCR recombinant expression, biochemistry, and crystallography. We describe our approach, ConDockSite, for predicting ligand binding sites in class A GPCRs using combined information from surface conservation and docking, starting from crystal structures or homology models. We demonstrate the effectiveness of ConDockSite on crystallized class A GPCRs such as the beta2 adrenergic and A2A adenosine receptors. We also demonstrate that ConDockSite successfully predicts ligand binding sites from high-quality homology models. Finally, we apply ConDockSite to predict the ligand binding sites on a structurally uncharacterized GPCR, GPER, the G-protein coupled estrogen receptor. Most of the sites predicted by ConDockSite match those found in other independent modeling studies. ConDockSite predicts that four ligands bind to a common location on GPER at a site deep in the receptor cleft. Incorporating sequence conservation information in ConDockSite overcomes errors introduced from physics-based scoring functions and homology modeling.
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Taghipour, Fatemeh, and Masoud Mirzaei. "A survey of interactions in crystal structures of pyrazine-based compounds." Acta Crystallographica Section C Structural Chemistry 75, no. 3 (February 15, 2019): 231–47. http://dx.doi.org/10.1107/s2053229619002225.
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The important role of pyrazine (pz) and its derivatives in fields such as biochemistry and pharmacology, as well as in the study of magnetic properties, is surveyed. Recognition of these properties without extensive investigations into their structural properties is not possible. This review summarizes interactions that exist between these organic compounds by themselves in the solid state, as well as those in coordination polymers with metal ions and in polyoxometalate-based hybrids. Complexes based on pyrazine ligands can generate metal–organic framework (MOF) structures that bind polyoxometalates (POMs) through covalent and noncovalent interactions. Some biological and magnetic properties involving these compounds are considered and the effect of hydrogen bonding on their supramolecular architectures is highlighted.
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Kovács, Béla, Előd Ernő Nagy, Norbert Nándor Chendrean, Blanka Székely-Szentmiklósi, and Árpád Gyéresi. "The Wnt Signalling Pathways: A Short Review and Specific Roles in Bone Biochemistry." Acta Medica Marisiensis 63, no. 3 (September 1, 2017): 104–9. http://dx.doi.org/10.1515/amma-2017-0026.
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AbstractAs musculoskeletal diseases become an emerging healthcare problem worldwide, profound and comprehensive research has been focused on the biochemistry of bone metabolism in the past decades. Wnt signalling, one of the novel described pathways influencing bone metabolism from the early stages of tissue development, has been recently in the centre of attention. Several Wnt ligands are implied in bone forming pathways via canonical (β-catenin dependent) and non-canonical (β-catenin independent) signalling. Osteoporosis, a catabolic bone disease, has its pathologic background related, inter alia, to alterations in the Wnt signalling, thus key modulators of these pathways became one of the most promising targets in the treatment of osteoporosis. Antibodies inhibiting the activity of endogenous Wnt pathway inhibitors (sclerostin, dickkopf) are recently under clinical trials. The current article offers a brief review of the Wnt signalling pathways, its implication in bone metabolism and fate, and the therapeutic possibilities of osteoporosis through Wnt signalling.
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Galassi, Rossana, Lorenzo Luciani, Junbiao Wang, Silvia Vincenzetti, Lishan Cui, Augusto Amici, Stefania Pucciarelli, and Cristina Marchini. "Breast Cancer Treatment: The Case of Gold(I)-Based Compounds as a Promising Class of Bioactive Molecules." Biomolecules 12, no. 1 (January 5, 2022): 80. http://dx.doi.org/10.3390/biom12010080.
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Breast cancers (BCs) may present dramatic diagnoses, both for ineffective therapies and for the limited outcomes in terms of lifespan. For these types of tumors, the search for new drugs is a primary necessity. It is widely recognized that gold compounds are highly active and extremely potent as anticancer agents against many cancer cell lines. The presence of the metal plays an essential role in the activation of the cytotoxicity of these coordination compounds, whose activity, if restricted to the ligands alone, would be non-existent. On the other hand, gold exhibits a complex biochemistry, substantially variable depending on the chemical environments around the central metal. In this review, the scientific findings of the last 6–7 years on two classes of gold(I) compounds, containing phosphane or carbene ligands, are reviewed. In addition to this class of Au(I) compounds, the recent developments in the application of Auranofin in regards to BCs are reported. Auranofin is a triethylphosphine-thiosugar compound that, being a drug approved by the FDA—therefore extensively studied—is an interesting lead gold compound and a good comparison to understand the activities of structurally related Au(I) compounds.
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Ramsay, Rona R., and Alen Albreht. "Questions in the Chemical Enzymology of MAO." Chemistry 3, no. 3 (August 31, 2021): 959–78. http://dx.doi.org/10.3390/chemistry3030069.
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We have structure, a wealth of kinetic data, thousands of chemical ligands and clinical information for the effects of a range of drugs on monoamine oxidase activity in vivo. We have comparative information from various species and mutations on kinetics and effects of inhibition. Nevertheless, there are what seem like simple questions still to be answered. This article presents a brief summary of existing experimental evidence the background and poses questions that remain intriguing for chemists and biochemists researching the chemical enzymology of and drug design for monoamine oxidases (FAD-containing EC 4.1.3.4).
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Sharma, Arun Kumar, Meenakshi Saxena, and Rashmi Sharma. "Fungicidal Activities and Characterization of Novel Biodegradable Cu (II) Surfactants Derived from Lauric Acid." Open Chemistry Journal 5, no. 1 (October 26, 2018): 89–101. http://dx.doi.org/10.2174/1874842201805010089.
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Introduction: Colloidal systems are extremely widespread in nature and are of great practical importance in our daily life. Surfactants are very important in modern engineering and pharmaceutical soap and the complexes of soaps with different ligands are used in almost all sectors of national economy due to the formation of micelles in solutions and high surface activity i.e. the ability of their molecules to form surface adsorption layers. For this purpose, first time we thought about the synthesis of copper surfactants/soaps and their complexation by N/S donor ligands. Methods and Materials: In this paper, we report the synthesis of copper laurate thiourea by conventional methods and its characterization by elemental analysis, IR, NMR, ESR spectral studies. In order to understand their biological aspects and application of these surfactants/complexes as antifungal agents, astudy has also been conducted in the field of biochemistry. In order to understand their biological aspects with special reference to fungicidal activities, three different fungi namely Aspergillus alternaria, Aspergillus Fumigatus and Aspergillus niger were taken and tested by different concentrations of copper laurate soap and its thiourea complex by P.D.A. (Potato dextrose agar) technique. Conclusion: Biological studies of these compounds will also provide an important account of information about their industrial utilization.
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Moreno, Cláudia Jassica Gonçalves, Henriqueta Monalisa Farias, Rafael Medeiros, Talita Brito, Johny Oliveira, Francimar Lopes de Sousa, Mayara Jane Campos de Medeiros, et al. "Quantum Biochemistry Screening and In Vitro Evaluation of Leishmania Metalloproteinase Inhibitors." International Journal of Molecular Sciences 23, no. 15 (August 2, 2022): 8553. http://dx.doi.org/10.3390/ijms23158553.
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Leishmanolysin, also known as major promastigote protease (PSP) or gp63, is the most abundant surface glycoprotein of Leishmania spp., and has been extensively studied and recognized as the main parasite virulence factor. Characterized as a metalloprotease, gp63 can be powerfully inactivated in the presence of a metal chelator. In this study, we first used the structural parameters of a 7-hydroxycoumarin derivative, L1 compound, to evaluate the theoretical–computational experiments against gp63, comparing it with an available metal chelator already described. The methodology followed was (i) analysis of the three-dimensional structure of gp63 as well as its active site, and searching the literature and molecular databases for possible inhibitors; (ii) molecular docking simulations and investigation of the interactions in the generated protein–ligand complexes; and (iii) the individual energy of the gp63 amino acids that interacted most with the ligands of interest was quantified by ab initio calculations using Molecular Fraction with Conjugated Caps (MFCC). MFCC still allowed the final quantum balance calculations of the protein interaction to be obtained with each inhibitor candidate binder. L1 obtained the best energy quantum balance result with −2 eV, followed by DETC (−1.4 eV), doxycycline (−1.3 eV), and 4-terpineol (−0.6 eV), and showed evidence of covalent binding in the enzyme active site. In vitro experiments confirmed L1 as highly effective against L. amazonensis parasites. The compound also exhibited a low cytotoxicity profile against mammalian RAW and 3T3 cells lines, presenting a selective index of 149.19 and 380.64 µM, respectively. L1 induced promastigote forms’ death by necrosis and the ultrastructural analysis revealed disruption in membrane integrity. Furthermore, leakage of the contents and destruction of the parasite were confirmed by Spectroscopy Dispersion analysis. These results together suggested L1 has a potential effect against L. amazonensis, the etiologic agent of diffuse leishmaniasis, and the only one that currently does not have a satisfactory treatment.
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Henry, J. P., D. Botton, C. Sagne, M. F. Isambert, C. Desnos, V. Blanchard, R. Raisman-Vozari, E. Krejci, J. Massoulie, and B. Gasnier. "Biochemistry and molecular biology of the vesicular monoamine transporter from chromaffin granules." Journal of Experimental Biology 196, no. 1 (November 1, 1994): 251–62. http://dx.doi.org/10.1242/jeb.196.1.251.
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Prior to secretion, monoamines (catecholamines, serotonin, histamine) are concentrated from the cytoplasm into vesicles by vesicular monoamine transporters (VMAT). These transporters also carry non-physiological compounds, e.g. the neurotoxin methyl-4-phenylpyridinium. VMAT acts as an electrogenic antiporter (exchanger) of protons and monoamines, using a proton electrochemical gradient. Vesicular transport is inhibited by specific ligands, including tetrabenazine, ketanserin and reserpine. The mechanism of transport and the biochemistry of VMAT have been analyzed with the help of these tools, using mainly the chromaffin granules from bovine adrenal glands as a source of transporter. Although biochemical studies did not suggest a multiplicity of VMATs, two homologous but distinct VMAT genes have recently been cloned from rat, bovine and human adrenal glands. The VMAT proteins are predicted to possess 12 transmembrane segments, with both extremities lying on the cytoplasmic side. They possess N-glycosylation sites in a putative luminal loop and phosphorylation sites in cytoplasmic domains. In rat, VMAT1 is expressed in the adrenal gland whereas VMAT2 is expressed in the brain. In contrast, we found that the bovine adrenal gland expressed both VMAT1 and VMAT2. VMAT2 corresponds to the major transporter of chromaffin granules, as shown by partial peptidic sequences of the purified protein and by a pharmacological analysis of the transport obtained in transfected COS cells (COS cells are monkey kidney cells possessing the ability to replicate SV-40-origin-containing plasmids). We discuss the possibility that VMAT1 may be specifically addressed to large secretory granules vesicles, whereas VMAT2 may also be addressed to small synaptic vesicles; species differences would then reflect the distinct physiological roles of the small synaptic vesicles in the adrenal gland.
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Duxbury, Zane, Chih-hang Wu, and Pingtao Ding. "A Comparative Overview of the Intracellular Guardians of Plants and Animals: NLRs in Innate Immunity and Beyond." Annual Review of Plant Biology 72, no. 1 (June 17, 2021): 155–84. http://dx.doi.org/10.1146/annurev-arplant-080620-104948.
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Nucleotide-binding domain leucine-rich repeat receptors (NLRs) play important roles in the innate immune systems of both plants and animals. Recent breakthroughs in NLR biochemistry and biophysics have revolutionized our understanding of how NLR proteins function in plant immunity. In this review, we summarize the latest findings in plant NLR biology and draw direct comparisons to NLRs of animals. We discuss different mechanisms by which NLRs recognize their ligands in plants and animals. The discovery of plant NLR resistosomes that assemble in a comparable way to animal inflammasomes reinforces the striking similarities between the formation of plant and animal NLR complexes. Furthermore, we discuss the mechanisms by which plant NLRs mediate immune responses and draw comparisons to similar mechanisms identified in animals. Finally, we summarize the current knowledge of the complex genetic architecture formed by NLRs in plants and animals and the roles of NLRs beyond pathogen detection.
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Liu, Hai Xing, Hua Mei Guo, Jing Zhong Xiao, Guang Zeng, Hui Juan Yue, and Xi Shi Tai. "Study on Novel Structure of Mn-Di(3,4,6,7-tetramethyl-1,10-phenanthroline) Dichloride: [Mn(C16H16N2)2]·Cl2." Key Engineering Materials 531-532 (December 2012): 413–16. http://dx.doi.org/10.4028/www.scientific.net/kem.531-532.413.
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Metal complexes containing diimine ligands such as 1,10-phenanthroline and bipyridine are very important and widely used in analytical chemistry, catalysis, electrochemistry, ring-opening metathesis polymerization and biochemistry. 1,10-phenanthroline, which is the parent for important class chelating agents, has been widely used in the construction of supramolecular architectures. Lots of phenanthroline and its derivatives complex have been synthesized and reported. In the paper, a novel Mn and 3,4,6,7-tetramethyl-1,10-phenanthroline complex [Mn(C16H16N2)2] •Cl2 has been synthesized from a solution reaction and the crystal structure has been determined by means of single-crystal X-ray diffraction. [Mn(C16H16N2)2] •Cl2, Orthorhombic, Pnna. a = 8.8376(8)Å b = 18.3630(17)Å c = 18.0159(18)Å α=β=γ=90°. V= 2923.7(5)Å3. Z=4. Rgt(F) = 0.0341, wRref(F2) = 0.0958. T= 273(2) K. The novel Mn metal complex structure is explained clearly.
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Keikha, Mojtaba, Mehrdad Pourayoubi, Atekeh Tarahhomi, and Arie van der Lee. "Syntheses and structures of four new mixed-amide phosphoric triamides." Acta Crystallographica Section C Structural Chemistry 72, no. 3 (February 29, 2016): 251–59. http://dx.doi.org/10.1107/s2053229616001595.
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Phosphoric triamides have extensive applications in biochemistry and are also used asO-donor ligands. Four new mixed-amide phosphoric triamide structures, namelyrac-N-tert-butyl-N′,N′′-dicyclohexyl-N′′-methylphosphoric triamide, C17H36N3OP, (I),rac-N,N′-dicyclohexyl-N′-methyl-N′′-(p-tolyl)phosphoric triamide, C20H34N3OP, (II),N,N′,N′′-tricyclohexyl-N′′-methylphosphoric triamide, C19H38N3OP, (III), and 2-[cyclohexyl(methyl)amino]-5,5-dimethyl-1,3,2λ5-diazaphosphinan-2-one, C12H26N3OP, (IV), have been synthesized and studied by X-ray diffraction and spectroscopic methods. Structures (I) and (II) are the first diffraction studies of acyclic racemic mixed-amide phosphoric triamides. The P—N bonds resulting from the different substituent –N(CH3)(C6H11), (C6H11)NH–, 4-CH3-C6H4NH–, (tert-C4H9)NH– and –NHCH2C(CH3)2CH2NH– groups are compared, along with the different molecular volumes and electron-donor strengths. In all four structures, the molecules form extended chains through N—H...O hydrogen bonds.
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Nagyal, Little, Amit Kumar, Rishipal Sharma, Rohit Yadav, Pratibha Chaudhary, and Rajeev Singh. "Bioinorganic Chemistry of Platinum(IV) Complexes as Platforms for Anticancer Agents." Current Bioactive Compounds 16, no. 6 (October 2, 2020): 726–37. http://dx.doi.org/10.2174/1573407215666190409105351.
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The current review focuses on the comprehensive studies of platinum-based complexes that are known to exhibit anticancer properties. The research on metal-particle work has helped in treating sicknesses which plays an imperative part in therapeutic bioinorganic science. Understanding the biochemistry of the detoxification mechanism of metals can help in advancing as well as enhancing the anticancer property of metal complexes for several types of a tumour. The classifications of complexes discussed have been done on the basis of Platinum oxidation states and binding sites of the ligands. Further background and current status of Pt(IV) complexes are briefly explained along with a special reference to Structural Activity Relationships and Mode of Action. The coordination chemistry of Pt(IV) has been summarised and Pt(IV) complexes are reviewed on the basis of binding of Pt(IV) with Human Serum Albumin and DNA. Finally, the results were summarized and concluded emphasizing on the most important features.
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Lazarova, Mariya, Younghoon Kim, and Alexander Steinle. "The NKG2D ligand ULBP4 is not expressed by human monocytes." PLOS ONE 16, no. 2 (February 8, 2021): e0246726. http://dx.doi.org/10.1371/journal.pone.0246726.
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The C-type lectin-like receptor NKG2D contributes to the immunosurveillance of virally infected and malignant cells by cytotoxic lymphocytes. A peculiar and puzzling feature of the NKG2D-based immunorecognition system is the high number of ligands for this single immunoreceptor. In humans, there are a total of eight NKG2D ligands (NKG2DL) comprising two members of the MIC (MICA, MICB) and six members of the ULBP family of glycoproteins (ULBP1 to ULBP6). While MICA has been extensively studied with regard to its biochemistry, cellular expression and function, very little is known about the NKG2DL ULBP4. This is, at least in part, due to its rather restricted expression by very few cell lines and tissues. Recently, constitutive ULBP4 expression by human monocytes was reported, questioning the view of tissue-restricted ULBP4 expression. Here, we scrutinized ULBP4 expression by human peripheral blood mononuclear cells and monocytes by analyzing ULBP4 transcripts and ULBP4 surface expression. In contrast to MICA, there was no ULBP4 expression detectable, neither by freshly isolated monocytes nor by PAMP-activated monocytes. However, a commercial antibody erroneously indicated surface ULBP4 on monocytes due to a non-ULBP4-specific binding activity, emphasizing the critical importance of validated reagents for life sciences. Collectively, our data show that ULBP4 is not expressed by monocytes, and likely also not by other peripheral blood immune cells, and therefore exhibits an expression pattern rather distinct from other human NKG2DL.
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Vazquez-Laslop, N., E. E. Zheleznova, P. N. Markham, R. G. Brennan, and A. A. Neyfakh. "Recognition of multiple drugs by a single protein: a trivial solution of an old paradox." Biochemical Society Transactions 28, no. 4 (August 1, 2000): 517–20. http://dx.doi.org/10.1042/bst0280517.
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Multi drug-efflux transporters recognize scores of structurally dissimilar toxic compounds and expel them from cells. The broad chemical specificity of these transporters challenges some of the basic dogmas of biochemistry and remains unexplained. To understand, at least in principle, how a protein can recognize multiple compounds, we analysed the transcriptional regulator of the Bacillus subtilis multidrug transporter Bmr. This regulator, BmrR, binds multiple dissimilar hydrophobic cations and, by activating the expression of the Bmr transporter, causes their expulsion from the cell. Crystallographic analysis of the complexes of the inducer-binding domain of BmrR with some of its inducers revealed that ligands cause disordering of the surface α-helix and penetrate the hydrophobic core of the protein, where they form multiple van der Waals and stacking interactions with hydrophobic amino acids and an electrostatic bond with the buried glutamic residue. Mutational analysis of the binding site suggests that each ligand forms a unique set of atomic contacts with the protein: each tested mutation exerted disparate effects on the binding of different ligands. The example of BmrR demonstrates that a protein can bind multiple compounds with micromolar affinities by using only electrostatic and hydrophobic interactions. Its ligand specificity can be broadened by the flexibility of the binding site. It therefore seems that the commonly expressed fascination with the broad specificity of multidrug transporters is misdirected and originates from an almost exclusive familiarity with the more sophisticated processes of specific molecular recognition that predominate among existing proteins.
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Cottet, Martin, Orestis Faklaris, Amadine Falco, Eric Trinquet, Jean-Philippe Pin, Bernard Mouillac, and Thierry Durroux. "Fluorescent ligands to investigate GPCR binding properties and oligomerization." Biochemical Society Transactions 41, no. 1 (January 29, 2013): 148–53. http://dx.doi.org/10.1042/bst20120237.
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Fluorescent ligands for GPCRs (G-protein-coupled receptors) have been synthesized for a long time but their use was usually restricted to receptor localization in the cell by fluorescent imaging microscopy. During the last two decades, the emergence of new fluorescence-based strategies and the concomitant development of fluorescent measurement apparatus have dramatically widened the use of fluorescent ligands. Among the various strategies, TR (time-resolved)-FRET (fluorescence resonance energy transfer) approaches exhibit an interesting potential to study GPCR interactions with various partners. We have derived various sets of ligands that target different GPCRs with fluorophores, which are compatible with TR-FRET strategies. Fluorescent ligands labelled either with a fluorescent donor (such as europium or terbium cryptate) or with a fluorescent acceptor (such as fluorescein, dy647 or Alexa Fluor® 647), for example, kept high affinities for their cognate receptors. These ligands turn out to be interesting tools to develop FRET-based binding assays. We also used these fluorescent ligands to analyse GPCR oligomerization by measuring FRET between ligands bound to receptor dimers. In contrast with FRET strategies, on the basis of receptor labelling, the ligand-based approach we developed is fully compatible with the study of wild-type receptors and therefore with receptors expressed in native tissues. Therefore, by using fluorescent analogues of oxytocin, we demonstrated the existence of oxytocin receptor dimers in the mammary gland of lactating rats.
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Nimjee, Shahid M., and Bruce A. Sullenger. "Therapeutic Aptamers: Evolving to Find their Clinical Niche." Current Medicinal Chemistry 27, no. 25 (July 22, 2020): 4181–93. http://dx.doi.org/10.2174/0929867326666191001125101.
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Background: The discovery that short oligonucleotides, termed aptamers, can fold into three-dimensional structures that allow them to selectively bind and inhibit the activity of pathogenic proteins is now over 25 years old. The invention of the SELEX methodology heralded in an era in which such nucleic acid-based ligands could be generated against a wide variety of therapeutic targets. Results: A large number of aptamers have now been identified by combinatorial chemistry methods in the laboratory and moreover, an increasing number have been discovered in nature. The affinities and activities of such aptamers have often been compared to that of antibodies, yet only a few of these agents have made it into clinical studies compared to a large and increasing number of therapeutic antibodies. One therapeutic aptamer targeting VEGF has made it to market, while 3 others have advanced as far as phase III clinical trials. Conclusion: In this manuscript, we hope the reader appreciates that the success of aptamers becoming a class of drugs is less about nucleic acid biochemistry and more about target validation and overall drug chemistry.
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Anand, Praveen, Deepesh Nagarajan, Sumanta Mukherjee, and Nagasuma Chandra. "ABS–Scan: In silico alanine scanning mutagenesis for binding site residues in protein–ligand complex." F1000Research 3 (September 9, 2014): 214. http://dx.doi.org/10.12688/f1000research.5165.1.
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Most physiological processes in living systems are fundamentally regulated by protein–ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ΔΔG values are computed by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide clues to researchers about residues to obtain loss-of-function mutations and to understand drug resistant mutations. This web-tool can be freely accessed through the following address: http://proline.biochem.iisc.ernet.in/abscan/.
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Anand, Praveen, Deepesh Nagarajan, Sumanta Mukherjee, and Nagasuma Chandra. "ABS–Scan: In silico alanine scanning mutagenesis for binding site residues in protein–ligand complex." F1000Research 3 (December 1, 2014): 214. http://dx.doi.org/10.12688/f1000research.5165.2.
Full textAbstract:
Most physiological processes in living systems are fundamentally regulated by protein–ligand interactions. Understanding the process of ligand recognition by proteins is a vital activity in molecular biology and biochemistry. It is well known that the residues present at the binding site of the protein form pockets that provide a conducive environment for recognition of specific ligands. In many cases, the boundaries of these sites are not well defined. Here, we provide a web-server to systematically evaluate important residues in the binding site of the protein that contribute towards the ligand recognition through in silico alanine-scanning mutagenesis experiments. Each of the residues present at the binding site is computationally mutated to alanine. The ligand interaction energy is computed for each mutant and the corresponding ΔΔG values are calculated by comparing it to the wild type protein, thus evaluating individual residue contributions towards ligand interaction. The server will thus provide a ranked list of residues to the user in order to obtain loss-of-function mutations. This web-tool can be freely accessed through the following address: http://proline.biochem.iisc.ernet.in/abscan/.
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Wise, Courtney E., Anastasia E. Ledinina, and Carolyn E. Lubner. "Site-Differentiated Iron–Sulfur Cluster Ligation Affects Flavin-Based Electron Bifurcation Activity." Metabolites 12, no. 9 (September 1, 2022): 823. http://dx.doi.org/10.3390/metabo12090823.
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Electron bifurcation is an elegant mechanism of biological energy conversion that effectively couples three different physiologically relevant substrates. As such, enzymes that perform this function often play critical roles in modulating cellular redox metabolism. One such enzyme is NADH-dependent reduced-ferredoxin: NADP+ oxidoreductase (NfnSL), which couples the thermodynamically favorable reduction of NAD+ to drive the unfavorable reduction of ferredoxin from NADPH. The interaction of NfnSL with its substrates is constrained to strict stoichiometric conditions, which ensures minimal energy losses from non-productive intramolecular electron transfer reactions. However, the determinants for this are not well understood. One curious feature of NfnSL is that both initial acceptors of bifurcated electrons are unique iron–sulfur (FeS) clusters containing one non-cysteinyl ligand each. The biochemical impact and mechanistic roles of site-differentiated FeS ligands are enigmatic, despite their incidence in many redox active enzymes. Herein, we describe the biochemical study of wild-type NfnSL and a variant in which one of the site-differentiated ligands has been replaced with a cysteine. Results of dye-based steady-state kinetics experiments, substrate-binding measurements, biochemical activity assays, and assessments of electron distribution across the enzyme indicate that this site-differentiated ligand in NfnSL plays a role in maintaining fidelity of the coordinated reactions performed by the two electron transfer pathways. Given the commonality of these cofactors, our findings have broad implications beyond electron bifurcation and mechanistic biochemistry and may inform on means of modulating the redox balance of the cell for targeted metabolic engineering approaches.
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Garratt, R. C., R. W. Evans, S. S. Hasnain, P. F. Lindley, and R. Sarra. "X.a.f.s. studies of chicken dicupric ovotransferrin." Biochemical Journal 280, no. 1 (November 15, 1991): 151–55. http://dx.doi.org/10.1042/bj2800151.
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A comparison of Cu K-edge x.a.f.s. spectra with that of the equivalent Fe K-edge for chicken ovotransferrin (COT) indicates that the metal ions occupy essentially the same binding sites in the protein. However, in the case of the Cu2+ complex the metal appears to have reduced co-ordination. Changes are observed in the x.a.f.s. of 90%-saturated COT (Cu1.8COT) on freeze-drying. The three-dimensional X-ray structures of rabbit serum transferrin and human lactoferrin have shown that the ferric cations are co-ordinated by four protein ligands and a bidentate carbonate anion in a distorted octahedral arrangement [Anderson, Baker, Dodson, Norris, Rumball, Waters & Baker (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 1768-1774; Anderson, Baker, Norris, Rice and Baker (1989) J. Mol. Biol. 209, 711-734; Bailey, Evans, Garratt, Gorinsky, Hasnain, Horsburgh, Jhoti, Lindley, Mydin, Sarra & Watson (1988) Biochemistry 27, 5804-5812]. This structural information, together with the differences in e.x.a.f.s. spectra for solution and freeze-dried samples of diferric COT [Hasnain, Evans, Garratt & Lindley (1987) Biochem. J. 247, 369-375] suggests that the synergistic carbonate anion may be capable of behaving as a unidentate linkage to the Cu2+ in the dicupric complex. Data for Cu1.8COT are consistent with only three protein ligands bound to Cu2+, monodentate binding of the synergistic anion in one lobe and its bidentate binding in the other lobe. Such flexibility in the anion co-ordination may be a requirement for the uptake and release of metals by the transferrins.
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Presley, Chaela S., Ammaar H. Abidi, and Bob M. Moore. "Corrigendum to ‘Cannabinoid receptor 1 ligands revisited: Pharmacological assessment in the ACTOne system’ [Analytical Biochemistry 498 (2016) 8–28]." Analytical Biochemistry 501 (May 2016): 47. http://dx.doi.org/10.1016/j.ab.2016.03.002.
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Kontoghiorghes, George, and Christina Kontoghiorghe. "Iron and Chelation in Biochemistry and Medicine: New Approaches to Controlling Iron Metabolism and Treating Related Diseases." Cells 9, no. 6 (June 12, 2020): 1456. http://dx.doi.org/10.3390/cells9061456.
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Iron is essential for all living organisms. Many iron-containing proteins and metabolic pathways play a key role in almost all cellular and physiological functions. The diversity of the activity and function of iron and its associated pathologies is based on bond formation with adjacent ligands and the overall structure of the iron complex in proteins or with other biomolecules. The control of the metabolic pathways of iron absorption, utilization, recycling and excretion by iron-containing proteins ensures normal biologic and physiological activity. Abnormalities in iron-containing proteins, iron metabolic pathways and also other associated processes can lead to an array of diseases. These include iron deficiency, which affects more than a quarter of the world’s population; hemoglobinopathies, which are the most common of the genetic disorders and idiopathic hemochromatosis. Iron is the most common catalyst of free radical production and oxidative stress which are implicated in tissue damage in most pathologic conditions, cancer initiation and progression, neurodegeneration and many other diseases. The interaction of iron and iron-containing proteins with dietary and xenobiotic molecules, including drugs, may affect iron metabolic and disease processes. Deferiprone, deferoxamine, deferasirox and other chelating drugs can offer therapeutic solutions for most diseases associated with iron metabolism including iron overload and deficiency, neurodegeneration and cancer, the detoxification of xenobiotic metals and most diseases associated with free radical pathology.
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Dimitroff, Charles J., Jack Y. Lee, Kenneth S. Schor, Brenda M. Sandmaier, and Robert Sackstein. "Differential L-Selectin Binding Activities of Human Hematopoietic Cell L-Selectin Ligands, HCELL and PSGL-1." Journal of Biological Chemistry 276, no. 50 (October 8, 2001): 47623–31. http://dx.doi.org/10.1074/jbc.m105997200.
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Expression of L-selectin on human hematopoietic cells (HC) is associated with a higher proliferative activity and a more rapid engraftment after hematopoietic stem cell transplantation. Two L-selectin ligands are expressed on human HCs, P-selectin glycoprotein ligand-1 (PSGL-1) and a specialized glycoform of CD44 (hematopoietic cell E- and L-selectin ligand, HCELL). Although the structural biochemistry of HCELL and PSGL-1 is well characterized, the relative capacity of these molecules to mediate L-selectin-dependent adhesion has not been explored. In this study, we examined under shear stress conditions L-selectin-dependent leukocyte adhesive interactions mediated by HCELL and PSGL-1, both as naturally expressed on human HC membranes and as purified molecules. By utilizing both Stamper-Woodruff and parallel-plate flow chamber assays, we found that HCELL displayed a 5-fold greater capacity to support L-selectin-dependent leukocyte adherence across a broad range of shear stresses compared with that of PSGL-1. Moreover, L-selectin-mediated leukocyte binding to immunopurified HCELL was consistently >5-fold higher than leukocyte binding to equivalent amounts of PSGL-1. Taken together, these data indicate that HCELL is a more avid L-selectin ligand than PSGL-1 and may be the preferential mediator of L-selectin-dependent adhesive interactions among human HCs in the bone marrow.
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Kinana, Alfred D., Attilio V. Vargiu, and Hiroshi Nikaido. "Some Ligands Enhance the Efflux of Other Ligands by theEscherichia coliMultidrug Pump AcrB." Biochemistry 52, no. 46 (November 11, 2013): 8342–51. http://dx.doi.org/10.1021/bi401303v.
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Yuan, Xiao-Chen, and Ya-Xiong Tao. "Ligands for Melanocortin Receptors: Beyond Melanocyte-Stimulating Hormones and Adrenocorticotropin." Biomolecules 12, no. 10 (October 1, 2022): 1407. http://dx.doi.org/10.3390/biom12101407.
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The discovery of melanocortins in 1916 has resulted in more than 100 years of research focused on these peptides. Extensive studies have elucidated well-established functions of melanocortins mediated by cell surface receptors, including MSHR (melanocyte-stimulating hormone receptor) and ACTHR (adrenocorticotropin receptor). Subsequently, three additional melanocortin receptors (MCRs) were identified. Among these five MCRs, MC3R and MC4R are expressed primarily in the central nervous system, and are therefore referred to as the neural MCRs. Since the central melanocortin system plays important roles in regulating energy homeostasis, targeting neural MCRs is emerging as a therapeutic approach for treating metabolic conditions such as obesity and cachexia. Early efforts modifying endogenous ligands resulted in the development of many potent and selective ligands. This review focuses on the ligands for neural MCRs, including classical ligands (MSH and agouti-related peptide), nonclassical ligands (lipocalin 2, β-defensin, small molecules, and pharmacoperones), and clinically approved ligands (ACTH, setmelanotide, bremelanotide, and several repurposed drugs).