Journal articles: 'Binding and catalysis'

1

Williams, Ian H. "Catalysis: transition-state molecular recognition?" Beilstein Journal of Organic Chemistry 6 (November 3, 2010): 1026–34. http://dx.doi.org/10.3762/bjoc.6.117.

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The key to understanding the fundamental processes of catalysis is the transition state (TS): indeed, catalysis is a transition-state molecular recognition event. Practical objectives, such as the design of TS analogues as potential drugs, or the design of synthetic catalysts (including catalytic antibodies), require prior knowledge of the TS structure to be mimicked. Examples, both old and new, of computational modelling studies are discussed, which illustrate this fundamental concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl transferase are described and compared with those for a model reaction in water, as computed by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations. The case is discussed of molecular recognition in a xylanase enzyme that stabilises its sugar substrate in a (normally unfavourable) boat conformation and in which a single-atom mutation affects the free-energy of activation dramatically.

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ABBADI, Amine, Monika BRUMMEL, Burkhardt S. SCHüTT, Mary B. SLABAUGH, Ricardo SCHUCH, and Friedrich SPENER. "Reaction mechanism of recombinant 3-oxoacyl-(acyl-carrier-protein) synthase III from Cuphea wrightii embryo, a fatty acid synthase type II condensing enzyme." Biochemical Journal 345, no. 1 (December 17, 1999): 153–60. http://dx.doi.org/10.1042/bj3450153.

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A unique feature of fatty acid synthase (FAS) type II of higher plants and bacteria is 3-oxoacyl-[acyl-carrier-protein (ACP)] synthase III (KAS III), which catalyses the committing condensing reaction. Working with KAS IIIs from Cuphea seeds we obtained kinetic evidence that KAS III catalysis follows a Ping-Pong mechanism and that these enzymes have substrate-binding sites for acetyl-CoA and malonyl-ACP. It was the aim of the present study to identify these binding sites and to elucidate the catalytic mechanism of recombinant Cuphea wrightii KAS III, which we expressed in Escherichia coli. We engineered mutants, which allowed us to dissect the condensing reaction into three stages, i.e. formation of acyl-enzyme, decarboxylation of malonyl-ACP, and final Claisen condensation. Incubation of recombinant enzyme with [1-14C]acetyl-CoA-labelled Cys111, and the replacement of this residue by Ala and Ser resulted in loss of overall condensing activity. The Cys111Ser mutant, however, still was able to bind acetyl-CoA and to catalyse subsequent binding and decarboxylation of malonyl-ACP to acetyl-ACP. We replaced His261 with Ala and Arg and found that the former lost activity, whereas the latter retained overall condensing activity, which indicated a general-base action of His261. Double mutants Cys111Ser/His261Ala and Cys111Ser/His261Arg were not able to catalyse overall condensation, but the double mutant containing Arg induced decarboxylation of [2-14C]malonyl-ACP, a reaction indicating the role of His261 in general-acid catalysis. Finally, alanine scanning revealed the involvement of Arg150 and Arg306 in KAS III catalysis. The results offer for the first time a detailed mechanism for a condensing reaction catalysed by a FAS type II condensing enzyme.

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Khan, Mohammad Niyaz, and Ibrahim Isah Fagge. "Kinetics and Mechanism of Cationic Micelle/Flexible Nanoparticle Catalysis: A Review." Progress in Reaction Kinetics and Mechanism 43, no. 1 (March 2018): 1–20. http://dx.doi.org/10.3184/146867818x15066862094905.

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The aqueous surfactant (Surf) solution at [Surf] > cmc (critical micelle concentration) contains flexible micelles/nanoparticles. These particles form a pseudophase of different shapes and sizes where the medium polarity decreases as the distance increases from the exterior region of the interface of the Surf/H2O particle towards its furthest interior region. Flexible nanoparticles (FNs) catalyse a variety of chemical and biochemical reactions. FN catalysis involves both positive catalysis ( i.e. rate increase) and negative catalysis ( i.e. rate decrease). This article describes the mechanistic details of these catalyses at the molecular level, which reveals the molecular origin of these catalyses. Effects of inert counterionic salts (MX) on the rates of bimolecular reactions (with one of the reactants as reactive counterion) in the presence of ionic FNs/micelles may result in either positive or negative catalysis. The kinetics of cationic FN (Surf/MX/H2O)-catalysed bimolecular reactions (with nonionic and anionic reactants) provide kinetic parameters which can be used to determine an ion exchange constant or the ratio of the binding constants of counterions.

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4

Pitson, Stuart M., Paul A. B. Moretti, Julia R. Zebol, Reza Zareie, Claudia K. Derian, Andrew L. Darrow, Jenson Qi, et al. "The Nucleotide-binding Site of Human Sphingosine Kinase 1." Journal of Biological Chemistry 277, no. 51 (October 18, 2002): 49545–53. http://dx.doi.org/10.1074/jbc.m206687200.

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Sphingosine kinase catalyzes the formation of sphingosine 1-phosphate, a lipid second messenger that has been implicated in a number of agonist-driven cellular responses including mitogenesis, anti-apoptosis, and expression of inflammatory molecules. Despite the importance of sphingosine kinase, very little is known regarding its structure or mechanism of catalysis. Moreover, sphingosine kinase does not contain recognizable catalytic or substrate-binding sites, based on sequence motifs found in other kinases. Here we have elucidated the nucleotide-binding site of human sphingosine kinase 1 (hSK1) through a combination of site-directed mutagenesis and affinity labeling with the ATP analogue, FSBA. We have shown that Gly82of hSK1 is involved in ATP binding since mutation of this residue to alanine resulted in an enzyme with an ∼45-fold higherKm(ATP). We have also shown that Lys103is important in catalysis since an alanine substitution of this residue ablates catalytic activity. Furthermore, we have shown that this residue is covalently modified by FSBA. Our data, combined with amino acid sequence comparison, suggest a motif of SGDGX17–21K is involved in nucleotide binding in the sphingosine kinases. This motif differs in primary sequence from all previously identified nucleotide-binding sites. It does, however, share some sequence and likely structural similarity with the highly conserved glycine-rich loop, which is known to be involved in anchoring and positioning the nucleotide in the catalytic site of many protein kinases.

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5

Breslow, Ronald. "Bifunctional binding and catalysis." Supramolecular Chemistry 1, no. 2 (February 1993): 111–18. http://dx.doi.org/10.1080/10610279308040656.

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Oliveira, Maria Teresa, and Ji-Woong Lee. "Asymmetric Cation-Binding Catalysis." ChemCatChem 9, no. 3 (January 12, 2017): 377–84. http://dx.doi.org/10.1002/cctc.201601441.

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MacMillan, Fraser, and Carola Hunte. "Quinone binding and catalysis." Biochimica et Biophysica Acta (BBA) - Bioenergetics 1797, no. 12 (December 2010): 1841. http://dx.doi.org/10.1016/j.bbabio.2010.10.021.

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8

Zapata-Pérez, Rubén, Fernando Gil-Ortiz, Ana Belén Martínez-Moñino, Antonio Ginés García-Saura, Jordi Juanhuix, and Álvaro Sánchez-Ferrer. "Structural and functional analysis of Oceanobacillus iheyensis macrodomain reveals a network of waters involved in substrate binding and catalysis." Open Biology 7, no. 4 (April 2017): 160327. http://dx.doi.org/10.1098/rsob.160327.

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Macrodomains are ubiquitous conserved domains that bind or transform ADP-ribose (ADPr) metabolites. In humans, they are involved in transcription, X-chromosome inactivation, neurodegeneration and modulating PARP1 signalling, making them potential targets for therapeutic agents. Unfortunately, some aspects related to the substrate binding and catalysis of MacroD-like macrodomains still remain unclear, since mutation of the proposed catalytic aspartate does not completely abolish enzyme activity. Here, we present a functional and structural characterization of a macrodomain from the extremely halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiMacroD), related to hMacroD1/hMacroD2, shedding light on substrate binding and catalysis. The crystal structures of D40A, N30A and G37V mutants, and those with MES, ADPr and ADP bound, allowed us to identify five fixed water molecules that play a significant role in substrate binding. Closure of the β6–α4 loop is revealed as essential not only for pyrophosphate recognition, but also for distal ribose orientation. In addition, a novel structural role for residue D40 is identified. Furthermore, it is revealed that OiMacroD not only catalyses the hydrolysis of O -acetyl-ADP-ribose but also reverses protein mono-ADP-ribosylation. Finally, mutant G37V supports the participation of a substrate-coordinated water molecule in catalysis that helps to select the proper substrate conformation.

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Bearne, Stephen L. "Asymmetry in catalysis: ‘unidirectional’ amino acid racemases." Biochemist 43, no. 1 (January 22, 2021): 28–34. http://dx.doi.org/10.1042/bio_2020_101.

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d-Amino acids play widespread structural, functional and regulatory roles in organisms. These d-amino acids often arise through the stereoinversion of the more plentiful l-amino acids catalysed by amino acid racemases and epimerases. Such enzymes are of interest since many are recognized targets for the development of drugs or may be employed industrially in biotransformation reactions. Despite their enzyme–substrate complexes being diastereomers, some racemases and epimerases exhibit a kinetic pseudo-symmetry, binding their enantiomeric or epimeric substrate pairs with roughly equal affinities and catalyzing their stereoinversion with similar turnover numbers. In other cases, this kinetic pseudo-symmetry is absent or may be ‘broken’ by substitution of a catalytic Cys by Ser at the active site of cofactor-independent racemases and epimerases, or by altering the Brønsted base of the catalytic dyad that facilitates deprotonation of the Cys residue. Moreover, a natural Thr-containing l-Asp/Glu racemase was discovered that catalyses ‘unidirectional’ substrate turnover, unlike the typical bidirectional racemases and epimerases. These observations suggest that bidirectional Cys–Cys racemases may be re-engineered into ‘unidirectional’ racemases through substitution of the thiol by a hydroxyl group. Catalysis by such ‘unidirectional’ racemase precursors could then be optimized further by site-directed mutagenesis and directed evolution to furnish useful enzymes for biotechnological applications.

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10

Pusuluk, Onur, Tristan Farrow, Cemsinan Deliduman, Keith Burnett, and Vlatko Vedral. "Proton tunnelling in hydrogen bonds and its implications in an induced-fit model of enzyme catalysis." Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 474, no. 2218 (October 2018): 20180037. http://dx.doi.org/10.1098/rspa.2018.0037.

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The role of proton tunnelling in biological catalysis is investigated here within the frameworks of quantum information theory and thermodynamics. We consider the quantum correlations generated through two hydrogen bonds between a substrate and a prototypical enzyme that first catalyses the tautomerization of the substrate to move on to a subsequent catalysis, and discuss how the enzyme can derive its catalytic potency from these correlations. In particular, we show that classical changes induced in the binding site of the enzyme spreads the quantum correlations among all of the four hydrogen-bonded atoms thanks to the directionality of hydrogen bonds. If the enzyme rapidly returns to its initial state after the binding stage, the substrate ends in a new transition state corresponding to a quantum superposition. Open quantum system dynamics can then naturally drive the reaction in the forward direction from the major tautomeric form to the minor tautomeric form without needing any additional catalytic activity. We find that in this scenario the enzyme lowers the activation energy so much that there is no energy barrier left in the tautomerization, even if the quantum correlations quickly decay.

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Hasse, Dirk, Janne Hülsemann, Gunilla H. Carlsson, Karin Valegård, and Inger Andersson. "Structure and mechanism of piperideine-6-carboxylate dehydrogenase from Streptomyces clavuligerus." Acta Crystallographica Section D Structural Biology 75, no. 12 (November 22, 2019): 1107–18. http://dx.doi.org/10.1107/s2059798319014852.

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The core of β-lactam antibiotics originates from amino acids of primary metabolism in certain microorganisms. β-Lactam-producing bacteria, including Streptomyces clavuligerus, synthesize the precursor of the amino acid α-aminoadipic acid by the catabolism of lysine in two steps. The second reaction, the oxidation of piperideine-6-carboxylate (or its open-chain form α-aminoadipate semialdehyde) to α-aminoadipic acid, is catalysed by the NAD+-dependent enzyme piperideine-6-carboxylate dehydrogenase (P6CDH). This structural study, focused on ligand binding and catalysis, presents structures of P6CDH from S. clavuligerus in its apo form and in complexes with the cofactor NAD+, the product α-aminoadipic acid and a substrate analogue, picolinic acid. P6CDH adopts the common aldehyde dehydrogenase fold, consisting of NAD-binding, catalytic and oligomerization domains. The product binds in the oxyanion hole, close to the catalytic residue Cys299. Clear density is observed for the entire cofactor, including the nicotinamide riboside, in the binary complex. NAD+ binds in an extended conformation with its nicotinamide ring overlapping with the binding site of the carboxylate group of the product, implying that the conformation of the cofactor may change during catalysis. The binding site of the substrate analogue overlaps with that of the product, suggesting that the cyclic form of the substrate, piperideine-6-carboxylate, may be accepted as a substrate by the enzyme. The catalytic mechanism and the roles of individual residues are discussed in light of these results.

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12

Badarau, Adriana, Christian Damblon, and Michael I. Page. "The activity of the dinuclear cobalt-β-lactamase from Bacillus cereus in catalysing the hydrolysis of β-lactams." Biochemical Journal 401, no. 1 (December 11, 2006): 197–203. http://dx.doi.org/10.1042/bj20061002.

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Metallo-β-lactamases are native zinc enzymes that catalyse the hydrolysis of β-lactam antibiotics, but are also able to function with cobalt(II) and require one or two metal-ions for catalytic activity. The hydrolysis of cefoxitin, cephaloridine and benzylpenicillin catalysed by CoBcII (cobalt-substituted β-lactamase from Bacillus cereus) has been studied at different pHs and metal-ion concentrations. An enzyme group of pKa 6.52±0.1 is found to be required in its deprotonated form for metal-ion binding and catalysis. The species that results from the loss of one cobalt ion from the enzyme has no significant catalytic activity and is thought to be the mononuclear CoBcII. It appears that dinuclear CoBcII is the active form of the enzyme necessary for turnover, while the mononuclear CoBcII is only involved in substrate binding. The cobalt-substituted enzyme is a more efficient catalyst than the native enzyme for the hydrolysis of some β-lactam antibiotics suggesting that the role of the metal-ion is predominantly to provide the nucleophilic hydroxide, rather than to act as a Lewis acid to polarize the carbonyl group and stabilize the oxyanion tetrahedral intermediate.

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13

Jadhav, Amol P., Sang Yeon Park, Ji-Woong Lee, Hailong Yan, and Choong Eui Song. "Cooperative Asymmetric Cation-Binding Catalysis." Accounts of Chemical Research 54, no. 23 (November 16, 2021): 4319–33. http://dx.doi.org/10.1021/acs.accounts.1c00400.

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14

Hansen, David E., and Ronald T. Raines. "Binding energy and enzymatic catalysis." Journal of Chemical Education 67, no. 6 (June 1990): 483. http://dx.doi.org/10.1021/ed067p483.

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Cui, Yao, Jixian Wang, Lei Yu, Ying Xu, David J. Young, Haiyan Li, and Hongxi Li. "Construction of a (NNN)Ru-Incorporated Porous Organic Polymer with High Catalytic Activity for β-Alkylation of Secondary Alcohols with Primary Alcohols." Polymers 14, no. 2 (January 7, 2022): 231. http://dx.doi.org/10.3390/polym14020231.

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Solid supports functionalized with molecular metal catalysts combine many of the advantages of heterogeneous and homogeneous catalysis. A (NNN)Ru-incorporated porous organic polymer (POP-bp/bbpRuCl3) exhibited high catalytic efficiency and broad functional group tolerance in the C–C cross-coupling of secondary and primary alcohols to give β-alkylated secondary alcohols. This catalyst demonstrated excellent durability during successive recycling without leaching of Ru which is ascribed to the strong binding of the pincer ligands to the metal ions.

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Leslie, A. G. W., and J. E. Walker. "Structural model of F 1 –ATPase and the implications for rotary catalysis." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1396 (April 29, 2000): 465–71. http://dx.doi.org/10.1098/rstb.2000.0588.

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The crystal structure of bovine mitochondrial F 1 –ATPase is described. Several features of the structure are consistent with the binding change mechanism of catalysis, in which binding of substrates induces conformational changes that result in a high degree of cooperativity between the three catalytic sites. Furthermore, the structure also suggests that catalysis is accompanied by a physical rotation of the centrally placed γ–subunit relative to the approximately spherical α 3 β 3 sub–assembly.

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Tinker, Henry R., Malavika A. Bhide, Emanuele Magliocca, Thomas S. Miller, and Caroline E. Knapp. "Synthetic tethered silver nanoparticles on reduced graphene oxide for alkaline oxygen reduction catalysis." Journal of Materials Science 56, no. 11 (January 18, 2021): 6966–76. http://dx.doi.org/10.1007/s10853-020-05711-2.

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AbstractThere is currently an enormous drive to move away from the use of Pt group metals in catalysis, particularly for fuel cells, because of their increasing rarity and cost. Simultaneously, there have been advances in the application of graphene supported nanoparticular catalysts. However, these Pt-free, graphene supported catalysts can be complex to produce, show poor catalytic activity and degrade quickly due to particle agglomeration or isolation. Herein, we report a one-pot synthesis of silver nanoparticles (NPs) tethered to a reduced graphene oxide (rGO) template via organic linkages. This is one of the few silver precursor formations that have been combined with graphene oxide (GO) to simultaneously establish linkage binding sites, reduce GO and yield tethered nanoparticles. These materials are shown to efficiently catalyze the oxygen reduction reaction in alkaline environments, with aminoethanol linkages to 21.55 ± 2.88 nm Ag particles exhibiting the highest catalytic activity via the four-electron pathway. This method, therefore, offers a straightforward route to produce effective catalysts from inexpensive precursors, which could be developed further for significant industrial application. Graphical abstract

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Salgado-Polo, Fernando, and Anastassis Perrakis. "The Structural Binding Mode of the Four Autotaxin Inhibitor Types that Differentially Affect Catalytic and Non-Catalytic Functions." Cancers 11, no. 10 (October 16, 2019): 1577. http://dx.doi.org/10.3390/cancers11101577.

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Autotaxin (ATX) is a secreted lysophospholipase D, catalysing the conversion of lysophosphatidylcholine (LPC) to bioactive lysophosphatidic acid (LPA). LPA acts through two families of G protein-coupled receptors (GPCRs) controlling key cellular responses, and it is implicated in many physiological processes and pathologies. ATX, therefore, has been established as an important drug target in the pharmaceutical industry. Structural and biochemical studies of ATX have shown that it has a bimetallic nucleophilic catalytic site, a substrate-binding (orthosteric) hydrophobic pocket that accommodates the lipid alkyl chain, and an allosteric tunnel that can accommodate various steroids and LPA. In this review, first, we revisit what is known about ATX-mediated catalysis, crucially in light of allosteric regulation. Then, we present the known ATX catalysis-independent functions, including binding to cell surface integrins and proteoglycans. Next, we analyse all crystal structures of ATX bound to inhibitors and present them based on the four inhibitor types that are established based on the binding to the orthosteric and/or the allosteric site. Finally, in light of these data we discuss how mechanistic differences might differentially modulate the activity of the ATX-LPA signalling axis, and clinical applications including cancer.

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Loh, Tamalette, Kenan C. Murphy, and Martin G. Marinus. "Mutational Analysis of the MutH Protein fromEscherichia coli." Journal of Biological Chemistry 276, no. 15 (December 21, 2000): 12113–19. http://dx.doi.org/10.1074/jbc.m007935200.

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Site-directed mutagenesis was performed on several areas of MutH based on the similarity of MutH andPvuII structural models. The aims were to identify DNA-binding residues; to determine whether MutH has the same mechanism for DNA binding and catalysis asPvuII; and to localize the residues responsible for MutH stimulation by MutL. No DNA-binding residues were identified in the two flexible loop regions of MutH, although similar loops inPvuII are involved in DNA binding. Two histidines in MutH are in a similar position as two histidines (His-84 and His-85) inPvuII that signal for DNA binding and catalysis. These MutH histidines (His-112 and His-115) were changed to alanines, but the mutant proteins had wild-type activity bothin vivoandin vitro. The results indicate that the MutH signal for DNA binding and catalysis remains unknown. Instead, a lysine residue (Lys-48) was found in the first flexible loop that functions in catalysis together with the three presumed catalytic amino acids (Asp-70, Glu-77, and Lys-79). Two deletion mutations (MutHΔ224 and MutHΔ214) in the C-terminal end of the protein, localized the MutL stimulation region to five amino acids (Ala-220, Leu-221, Leu-222, Ala-223, and Arg-224).

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Cao, Liang, Le Niu, and Tim Mueller. "Computationally generated maps of surface structures and catalytic activities for alloy phase diagrams." Proceedings of the National Academy of Sciences 116, no. 44 (October 14, 2019): 22044–51. http://dx.doi.org/10.1073/pnas.1910724116.

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To facilitate the rational design of alloy catalysts, we introduce a method for rapidly calculating the structure and catalytic properties of a substitutional alloy surface that is in equilibrium with the underlying bulk phase. We implement our method by developing a way to generate surface cluster expansions that explicitly account for the lattice parameter of the bulk structure. This approach makes it possible to computationally map the structure of an alloy surface and statistically sample adsorbate binding energies at every point in the alloy phase diagram. When combined with a method for predicting catalytic activities from adsorbate binding energies, maps of catalytic activities at every point in the phase diagram can be created, enabling the identification of synthesis conditions likely to result in highly active catalysts. We demonstrate our approach by analyzing Pt-rich Pt–Ni catalysts for the oxygen reduction reaction, finding 2 regions in the phase diagram that are predicted to result in highly active catalysts. Our analysis indicates that the Pt3Ni(111) surface, which has the highest known specific activity for the oxygen reduction reaction, is likely able to achieve its high activity through the formation of an intermetallic phase with L12 order. We use the generated surface structure and catalytic activity maps to demonstrate how the intermetallic nature of this phase leads to high catalytic activity and discuss how the underlying principles can be used in catalysis design. We further discuss the importance of surface phases and demonstrate how they can dramatically affect catalytic activity.

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Raven, Emma L., Latesh Lad, Katherine H. Sharp, Martin Mewies, and Peter C. E. Moody. "Defining substrate specificity and catalytic mechanism in ascorbate peroxidase." Biochemical Society Symposia 71 (March 1, 2004): 27–38. http://dx.doi.org/10.1042/bss0710027.

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Haem peroxidases catalyse the H2O2-dependent oxidation of a variety of, usually organic, substrates. Mechanistically, these enzymes are very well characterized: they share a common catalytic cycle that involves formation of a two-electron oxidized intermediate (Compound I) followed by reduction of Compound I by substrate. The substrate specificity is more diverse, however. Most peroxidases oxidize small organic substrates, but there are prominent exceptions to this and the structural features that control substrate specificity remain poorly defined. APX (ascorbate peroxidase) catalyses the H2O2-dependent oxidation of l-ascorbate and has properties that place it at the interface between the class I (e.g. cytochrome c peroxidase) and classical class III (e.g. horseradish peroxidase) peroxidase enzymes. We present a unified analysis of the catalytic and substrate-binding properties of APX, including the crystal structure of the APX-ascorbate complex. Our results provide new rationalization of the unusual functional features of the related cytochrome c peroxidase enzyme, which has been a benchmark for peroxidase-mediated catalysis for more than 20 years.

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Chen, Yang, Joakim Näsvall, Shiying Wu, Dan I. Andersson, and Maria Selmer. "Structure of AadA fromSalmonella enterica: a monomeric aminoglycoside (3′′)(9) adenyltransferase." Acta Crystallographica Section D Biological Crystallography 71, no. 11 (October 31, 2015): 2267–77. http://dx.doi.org/10.1107/s1399004715016429.

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Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3′′)(9) adenyltransferase, AadA fromSalmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 Å resolution. AadA consists of a nucleotidyltransferase domain and an α-helical bundle domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis.In vivoresistance andin vitrobinding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding.

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Lagerbäck, Pernilla, and Karin Carlson. "Amino Acid Residues in the GIY-YIG Endonuclease II of Phage T4 Affecting Sequence Recognition and Binding as Well as Catalysis." Journal of Bacteriology 190, no. 16 (June 6, 2008): 5533–44. http://dx.doi.org/10.1128/jb.00094-08.

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ABSTRACT Phage T4 endonuclease II (EndoII), a GIY-YIG endonuclease lacking a carboxy-terminal DNA-binding domain, was subjected to site-directed mutagenesis to investigate roles of individual amino acids in substrate recognition, binding, and catalysis. The structure of EndoII was modeled on that of UvrC. We found catalytic roles for residues in the putative catalytic surface (G49, R57, E118, and N130) similar to those described for I-TevI and UvrC; in addition, these residues were found to be important for substrate recognition and binding. The conserved glycine (G49) and arginine (R57) were essential for normal sequence recognition. Our results are in agreement with a role for these residues in forming the DNA-binding surface and exposing the substrate scissile bond at the active site. The conserved asparagine (N130) and an adjacent proline (P127) likely contribute to positioning the catalytic domain correctly. Enzymes in the EndoII subfamily of GIY-YIG endonucleases share a strongly conserved middle region (MR, residues 72 to 93, likely helical and possibly substituting for heterologous helices in I-TevI and UvrC) and a less strongly conserved N-terminal region (residues 12 to 24). Most of the conserved residues in these two regions appeared to contribute to binding strength without affecting the mode of substrate binding at the catalytic surface. EndoII K76, part of a conserved NUMOD3 DNA-binding motif of homing endonucleases found to overlap the MR, affected both sequence recognition and catalysis, suggesting a more direct involvement in positioning the substrate. Our data thus suggest roles for the MR and residues conserved in GIY-YIG enzymes in recognizing and binding the substrate.

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Zhou, Yibo, Eui-Hyun Ryu, Yan Zhao, and L. Keith Woo. "Solvent-Responsive Metalloporphyrins: Binding and Catalysis." Organometallics 26, no. 2 (January 2007): 358–64. http://dx.doi.org/10.1021/om060791z.

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Zhao, Chenfei, Christopher A. Sojdak, Wazo Myint, and Daniel Seidel. "Reductive Etherification via Anion-Binding Catalysis." Journal of the American Chemical Society 139, no. 30 (July 25, 2017): 10224–27. http://dx.doi.org/10.1021/jacs.7b05832.

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Attard, Jonathan, Kohei Osawa, Yong Guan, Jessica Hatt, Shin-ichi Kondo, and Anita Mattson. "Silanediol Anion Binding and Enantioselective Catalysis." Synthesis 51, no. 10 (March 12, 2019): 2107–15. http://dx.doi.org/10.1055/s-0037-1612217.

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Silanediols possess unique and complementary catalytic activity in reactions that are likely to proceed through anion binding. This article directly compares silanediols, thioureas, and squaramides in three separate anion-binding processes. The catalytic abilities of select members of each family are directly correlated to association constants.

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Park, Sang Yeon, Yidong Liu, Joong Suk Oh, Yoo Kyung Kweon, Yong Bok Jeong, Mengying Duan, Yu Tan, Ji-Woong Lee, Hailong Yan, and Choong Eui Song. "Asymmetric Aminalization via Cation-Binding Catalysis." Chemistry - A European Journal 24, no. 5 (December 5, 2017): 1020–25. http://dx.doi.org/10.1002/chem.201703800.

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Schafer, Andrew G., Joshua M. Wieting, Thomas J. Fisher, and Anita E. Mattson. "Chiral Silanediols in Anion-Binding Catalysis." Angewandte Chemie 125, no. 43 (September 3, 2013): 11531–34. http://dx.doi.org/10.1002/ange.201305496.

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Schafer, Andrew G., Joshua M. Wieting, Thomas J. Fisher, and Anita E. Mattson. "Chiral Silanediols in Anion-Binding Catalysis." Angewandte Chemie International Edition 52, no. 43 (September 3, 2013): 11321–24. http://dx.doi.org/10.1002/anie.201305496.

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PATEL, Chandra N., David W. KOH, Myron K. JACOBSON, and Marcos A. OLIVEIRA. "Identification of three critical acidic residues of poly(ADP-ribose) glycohydrolase involved in catalysis: determining the PARG catalytic domain." Biochemical Journal 388, no. 2 (May 24, 2005): 493–500. http://dx.doi.org/10.1042/bj20040942.

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PARG [poly(ADP-ribose) glycohydrolase] catalyses the hydrolysis of α(1″→2′) or α(1‴→2″) O-glycosidic linkages of ADP-ribose polymers to produce free ADP-ribose. We investigated possible mechanistic similarities between PARG and glycosidases, which also cleave O-glycosidic linkages. Glycosidases typically utilize two acidic residues for catalysis, thus we targeted acidic residues within a conserved region of bovine PARG that has been shown to contain an inhibitor-binding site. The targeted glutamate and aspartate residues were changed to asparagine in order to minimize structural alterations. Mutants were purified and assayed for catalytic activity, as well as binding, to an immobilized PARG inhibitor to determine ability to recognize substrate. Our investigation revealed residues essential for PARG catalytic activity. Two adjacent glutamic acid residues are found in the conserved sequence Gln755-Glu-Glu757, and a third residue found in the conserved sequence Val737-Asp-Phe-Ala-Asn741. Our functional characterization of PARG residues, along with recent identification of an inhibitor-binding residue Tyr796 and a glycine-rich region Gly745-Gly-Gly747 important for PARG function, allowed us to define a PARG ‘signature sequence’ [vDFA-X3-GGg-X6–8-vQEEIRF-X3-PE-X14-E-X12-YTGYa], which we used to identify putative PARG sequences across a range of organisms. Sequence alignments, along with our mapping of PARG functional residues, suggest the presence of a conserved catalytic domain of approx. 185 residues which spans residues 610–795 in bovine PARG.

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HIGHTOWER, Kendra E., Smita DE, Carolyn WEINBAUM, Rebecca A. SPENCE, and Patrick J. CASEY. "Lysine164α of protein farnesyltransferase is important for both CaaX substrate binding and catalysis." Biochemical Journal 360, no. 3 (December 10, 2001): 625–31. http://dx.doi.org/10.1042/bj3600625.

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Protein farnesyltransferase (FTase) catalyses the formation of a thioether linkage between proteins containing a C-terminal CaaX motif and a 15-carbon isoprenoid. The involvement of substrates such as oncogenic Ras proteins in tumour formation has led to intense efforts in targeting this enzyme for development of therapeutics. In an ongoing programme to elucidate the mechanism of catalysis by FTase, specific residues of the enzyme identified in structural studies as potentially important in substrate binding and catalysis are being targeted for mutagenesis. In the present study, the role of the positive charge of Lys164 of the α subunit of FTase in substrate binding and catalysis was investigated. Comparison of the wild-type enzyme with enzymes that have either an arginine or alanine residue substituted at this position revealed unexpected roles for this residue in both substrate binding and catalysis. Removal of the positive charge had a significant effect on the association rate constant and the binding affinity of a CaaX peptide substrate, indicating that the positive charge of Lys164α is involved in formation of the enzyme (E)·farnesyl diphosphate (FPP)·peptide ternary complex. Furthermore, mutation of Lys164α resulted in a substantial decrease in the observed rate constant for product formation without alteration of the chemical mechanism. These and additional studies provide compelling evidence that both the charge on Lys164α, as well as the positioning of the charge, are important for overall catalysis by FTase.

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32

Chen, Yan-Liang, Yun-Hao Chou, Chia-Lin Hsieh, Shean-Jaw Chiou, Tzu-Pin Wang, and Chi-Ching Hwang. "Rational Engineering of 3α-Hydroxysteroid Dehydrogenase/Carbonyl Reductase for a Biomimetic Nicotinamide Mononucleotide Cofactor." Catalysts 12, no. 10 (September 21, 2022): 1094. http://dx.doi.org/10.3390/catal12101094.

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Enzymes are powerful biological catalysts for natural substrates but they have low catalytic efficiency for non-natural substrates. Protein engineering can be used to optimize enzymes for catalysis and stability. 3α-Hydroxysteroid dehydrogenase/carbonyl reductase (3α-HSD/CR) catalyzes the oxidoreduction reaction of NAD+ with androsterone. Based on the structure and catalytic mechanism, we mutated the residues of T11, I13, D41, A70, and I112 and they interacted with different portions of NAD+ to switch cofactor specificity to biomimetic cofactor nicotinamide mononucleotide (NMN+). Compared to wild-type 3α-HSD/CR, the catalytic efficiency of these mutants for NAD+ decreased significantly except for the T11 mutants but changed slightly for NMN+ except for the A70K mutant. The A70K mutant increased the catalytic efficiency for NMN+ by 8.7-fold, concomitant with a significant decrease in NAD+ by 1.4 × 104-fold, resulting in 9.6 × 104-fold cofactor specificity switch toward NMN+ over NAD+. Meanwhile, the I112K variant increased the thermal stability and changed to a three-state transition from a two-state transition of thermal unfolding of wild-type 3α-HSD/CR by differential scanning fluorimetry. Molecular docking analysis indicated that mutations on these residues affect the position and conformation of the docked NAD+ and NMN+, thereby affecting their activity. A70K variant sterically blocks the binding with NAD+, restores the H-bonding interactions of catalytic residues of Y155 and K159 with NMN+, and enhances the catalytic efficiency for NMN+.

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RESMINI, Marina, Sheraz GUL, Steve CARTER, Sanjiv SONKARIA, Christopher M. TOPHAM, Gerrard GALLACHER, and Keith BROCKLEHURST. "A general kinetic approach to investigation of active-site availability in macromolecular catalysts." Biochemical Journal 346, no. 1 (February 8, 2000): 117–25. http://dx.doi.org/10.1042/bj3460117.

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A potentially general kinetic method for the investigation of active-site availability in preparations of macromolecular catalysts was developed. Three kinetic models were considered: (a) the conventional two-step model of enzyme catalysis, where the preparation contains only active catalyst (Ea) and inert (i.e. non-binding, non-catalytic) material (Ei); (b) an extension of the conventional model (a) involving only Ea and Ei, but with non-productive binding to Ea (in addition to productive binding); (c) a model in which the preparation contains also binding but non-catalytic material (Eb), predicted to be present in polyclonal catalytic antibody preparations. The method involves comparing the parameters Vmax and Km obtained under catalytic conditions where substrate concentrations greatly exceed catalyst concentration with those (k, the limiting value of the first-order rate constant, kobs, at saturating concentrations of catalyst; and K) for single-turnover kinetics, in which the reverse situation obtains. The active-site contents of systems that adhere to model (a) or extensions that also lack Eb, such as the non-productive binding model (b), may be calculated using [Ea]T = Vmax/k. This was validated by showing that, for α-chymotrypsin, identical values of [Ea]T were obtained by the kinetic method using Suc-Ala-Ala-Pro-Phe-4-nitroanilide as substrate and the well-known ‘all-or-none’ spectroscopic assay using N-trans-cinnamoylimidazole as titrant. For systems that contain Eb, such as polyclonal catalytic antibody preparations, Vmax/k is more complex, but provides an upper limit to [Ea]T. Use of the kinetic method to investigate PCA 271-22, a polyclonal catalytic antibody preparation obtained from the antiserum of sheep 271 in week 22 of the immunization protocol, established that [Ea]T is less than approx. 8% of [IgG], and probably less than approx. 1% of [IgG].

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34

Chen, Aochiu, Jeffrey T. Mindrebo, Tony D. Davis, Woojoo E. Kim, Yohei Katsuyama, Ziran Jiang, Yasuo Ohnishi, Joseph P. Noel, and Michael D. Burkart. "Mechanism-based cross-linking probes capture the Escherichia coli ketosynthase FabB in conformationally distinct catalytic states." Acta Crystallographica Section D Structural Biology 78, no. 9 (August 30, 2022): 1171–79. http://dx.doi.org/10.1107/s2059798322007434.

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Ketosynthases (KSs) catalyse essential carbon–carbon bond-forming reactions in fatty-acid biosynthesis using a two-step, ping-pong reaction mechanism. In Escherichia coli, there are two homodimeric elongating KSs, FabB and FabF, which possess overlapping substrate selectivity. However, FabB is essential for the biosynthesis of the unsaturated fatty acids (UFAs) required for cell survival in the absence of exogenous UFAs. Additionally, FabB has reduced activity towards substrates longer than 12 C atoms, whereas FabF efficiently catalyses the elongation of saturated C14 and unsaturated C16:1 acyl-acyl carrier protein (ACP) complexes. In this study, two cross-linked crystal structures of FabB in complex with ACPs functionalized with long-chain fatty-acid cross-linking probes that approximate catalytic steps were solved. Both homodimeric structures possess asymmetric substrate-binding pockets suggestive of cooperative relationships between the two FabB monomers when engaged with C14 and C16 acyl chains. In addition, these structures capture an unusual rotamer of the active-site gating residue, Phe392, which is potentially representative of the catalytic state prior to substrate release. These structures demonstrate the utility of mechanism-based cross-linking methods to capture and elucidate conformational transitions accompanying KS-mediated catalysis at near-atomic resolution.

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35

EIS, Christian, and Bernd NIDETZKY. "Substrate-binding recognition and specificity of trehalose phosphorylase from Schizophyllum commune examined in steady-state kinetic studies with deoxy and deoxyfluoro substrate analogues and inhibitors." Biochemical Journal 363, no. 2 (April 8, 2002): 335–40. http://dx.doi.org/10.1042/bj3630335.

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Trehalose phosphorylase is a component of the α-d-glucopyranosyl α-d-glucopyranoside (α,α-trehalose)-degrading enzyme system in fungi and it catalyses glucosyl transfer from α,α-trehalose to phosphate with net retention of the anomeric configuration. The enzyme active site has no detectable affinity for α,α-trehalose in the absence of bound phosphate and catalysis occurs from the ternary complex. To examine the role of non-covalent enzyme—substrate interactions for trehalose phosphorylase recognition, we used the purified enzyme from Schizophyllum commune and tested a series of incompetent structural analogues of the natural substrates and products as inhibitors of the enzyme. Equilibrium-binding constants (Ki) for deoxy- and deoxyfluoro derivatives of d-glucose show that loss of interactions with the 3-, 4- or 6-OH, but not the reactive 1- and the 2-OH, results in considerably (≥100-fold) weaker affinity for sugar-binding subsite +1, revealing the requirement for hydrogen bonding with hydroxyls, away from the site of chemical transformation to position precisely the d-glucose-leaving group/nucleophile for catalysis. The high specificity of trehalose phosphorylase for the sugar aglycon during binding and conversion of O-glycosides is in contrast with the observed α-retaining phosphorolysis of α-d-glucose-1-fluoride (α-d-Glc-1-F) since the productive bonding capability of the fluoride-leaving group with subsite +1 is minimal. The specificity constant (19M−1·s−1) and catalytic-centre activity (0.1s−1) for the reaction with α-d-Glc-1-F are 0.10- and 0.008-fold the corresponding kinetic parameters for the enzymic reaction with α,α-trehalose. The non-selective-inhibition profile for a series of inactive α-d-glycopyranosyl phosphates shows that the driving force for the binary-complex formation lies mainly in interactions of the enzyme with the phosphate group and suggests that hydrogen bonding with hydroxyl groups at the catalytic site (subsite −1) contributes to catalysis by providing stabilization, which is specific to the transition state. Vanadate, a tight-binding phosphate mimic, inhibits the phosphorolysis of α-d-Glc-1-F by forming a ternary complex whose apparent dissociation constant of 120μM is approx. 160-fold greater than the dissociation constant of the same inhibitor complex with α,α-trehalose.

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36

ALLARDYCE, Claire S., Paul D. MCDONAGH, Lu-Yun LIAN, C. Roland WOLF, and Gordon C. K. ROBERTS. "The role of tyrosine-9 and the C-terminal helix in the catalytic mechanism of Alpha-class glutathione S-transferases." Biochemical Journal 343, no. 3 (October 25, 1999): 525–31. http://dx.doi.org/10.1042/bj3430525.

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Glutathione S-transferases (GSTs) play a key role in the metabolism of drugs and xenobiotics. To investigate the catalytic mechanism, substrate binding and catalysis by the wild-type and two mutants of GST A1-1 have been studied. Substitution of the ‘essential’ Tyr9 by phenylalanine leads to a marked decrease in the kcat for 1-chloro-2,4-dinitrobenzene (CDNB), but has no affect on kcat for ethacrynic acid. Similarly, removal of the C-terminal helix by truncation of the enzyme at residue 209 leads to a decrease in kcat for CDNB, but an increase in kcat for ethacrynic acid. The binding of a GSH analogue increases the affinity of the wild-type enzyme for CDNB, and increases the rate of the enzyme-catalysed conjugation of this substrate with the small thiols 2-mercaptoethanol and dithiothreitol. This suggests that GSH binding produces a conformational change which is transmitted to the binding site for the hydrophobic substrate, where it alters both the affinity for the substrate and the catalytic-centre activity (‘turnover number‘) for conjugation, perhaps by increasing the proportion of the substrate bound productively. Neither of these two effects of GSH analogues are seen in the C-terminally truncated enzyme, indicating a role for the C-terminal helix in the GSH-induced conformational change.

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37

Sebati, Wilhemina, and Suprakas Ray. "Advances in Nanostructured Metal-Encapsulated Porous Organic-Polymer Composites for Catalyzed Organic Chemical Synthesis." Catalysts 8, no. 11 (October 24, 2018): 492. http://dx.doi.org/10.3390/catal8110492.

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Porous organic polymers (POPs) are of growing research interest owing to their high surface areas, stabilities, controllable chemical configurations, and tunable pore volumes. The molecular nanoarchitecture of POP provides metal or metal oxide binding sites, which is promising for the development of advanced heterogeneous catalysts. This article highlights the development of numerous kinds of POPs and key achievements to date, including their functionalization and incorporation of nanoparticles into their framework structures, characterization methods that are predominantly in use for POP-based materials, and their applications as catalysts in several reactions. Scientists today are capable of preparing POP-based materials that show good selectivity, activity, durability, and recoverability, which can help overcome many of the current environmental and industrial problems. These POP-based materials exhibit enhanced catalytic activities for diverse reactions, including coupling, hydrogenation, and acid catalysis.

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38

Marcus, Yehouda, Hagit Altman-Gueta, Aliza Finkler, and Michael Gurevitz. "Mutagenesis at Two Distinct Phosphate-Binding Sites Unravels Their Differential Roles in Regulation of Rubisco Activation and Catalysis." Journal of Bacteriology 187, no. 12 (June 15, 2005): 4222–28. http://dx.doi.org/10.1128/jb.187.12.4222-4228.2005.

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ABSTRACT Orthophosphate (Pi) has two antagonistic effects on ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), stimulation of activation and inhibition of catalysis by competition with the substrate RuBP. The enzyme binds Pi at three distinct sites, two within the catalytic site (where 1P and 5P of ribulose 1,5-bisphosphate [RuBP] bind), and the third at the latch site (a positively charged pocket involved in active-site closure during catalysis). We examined the role of the latch and 5P sites in regulation of Rubisco activation and catalysis by introducing specific mutations in the enzyme of the cyanobacterium Synechocystis sp. strain PCC 6803. Whereas mutations at both sites abolished the Pi-stimulated Rubisco activation, substitution of residues at the 5P site, but not at the latch site, affected the Pi inhibition of Rubisco catalysis. Although some of these mutations substantially reduced the catalytic turnover of Rubisco and increased the Km (RuBP), they had little to moderate effect on the rate of photosynthesis and no effect on photoautotrophic growth. These findings suggest that in cyanobacteria, Rubisco does not limit photosynthesis to the extent previously estimated. These results indicate that both the latch and 5P sites participate in regulation of Rubisco activation, whereas Pi binding only at the 5P site inhibits catalysis in a competitive manner.

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Do, Hackwon, Dieu Linh Nguyen, Chang Woo Lee, Min Ju Lee, Hoejung Oh, Jisub Hwang, Se Jong Han, Sung Gu Lee, and Jun Hyuck Lee. "Comparative structural insight into the unidirectional catalysis of ornithine carbamoyltransferases from Psychrobacter sp. PAMC 21119." PLOS ONE 17, no. 9 (September 23, 2022): e0274019. http://dx.doi.org/10.1371/journal.pone.0274019.

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Ornithine carbamoyltransferases (OTCs) are involved in the arginine deiminase (ADI) pathway and in arginine biosynthesis. Two OTCs in a pair are named catalytic OTC (cOTC) and anabolic OTC (aOTC). The cOTC is responsible for catalyzing the third step of the ADI pathway to catabolize citrulline into carbamoyl phosphate (CP), as well as ornithine, and displays CP cooperativity. In contrast, aOTC catalyzes the biosynthesis of citrulline from CP and ornithine in vivo and is thus involved in arginine biosynthesis. Structural and biochemical analyses were employed to investigate the CP cooperativity and unidirectional function of two sequentially similar OTCs (32.4% identity) named Ps_cOTC and Ps_aOTC from Psychrobacter sp. PAMC 21119. Comparison of the trimeric structure of these two OTCs indicated that the 80s loop of Ps_cOTC has a unique conformation that may influence cooperativity by connecting the CP binding site and the center of the trimer. The corresponding 80s loop region of in Ps_aOTC was neither close to the CP binding site nor connected to the trimer center. In addition, results from the thermal shift assay indicate that each OTC prefers the substrate for the unidirectional process. The active site exhibited a blocked binding site for CP in the Ps_cOTC structure, whereas residues at the active site in Ps_aOTC established a binding site to facilitate CP binding. Our data provide novel insights into the unidirectional catalysis of OTCs and cooperativity, which are distinguishable features of two metabolically specialized proteins.

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40

D'AMOURS, Marc R., and Rick H. COTE. "Regulation of photoreceptor phosphodiesterase catalysis by its non-catalytic cGMP-binding sites." Biochemical Journal 340, no. 3 (June 8, 1999): 863–69. http://dx.doi.org/10.1042/bj3400863.

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The photoreceptor 3ʹ:5ʹ-cyclic nucleotide phosphodiesterase (PDE) is the central enzyme of visual excitation in rod photoreceptors. The hydrolytic activity of PDE is precisely regulated by its inhibitory γ subunit (Pγ), which binds directly to the catalytic site. We examined the inhibition of frog rod outer segment PDE by endogenous Pγ, as well as by synthetic peptides corresponding to its central and C-terminal domains, to determine whether the non-catalytic cGMP-binding sites on the catalytic αβ dimer of PDE allosterically regulate PDE activity. We found that the apparent binding affinity of Pγ for PDE was 28 pM when cGMP occupied the non-catalytic sites, whereas Pγ had an apparent affinity only 1/16 of this when the sites were empty. The elevated basal activity of PDE with empty non-catalytic sites can be decreased by the addition of nanomolar levels of cGMP, demonstrating that the high-affinity non-catalytic sites on the PDE catalytic dimer mediate this effect. No evidence for a direct allosteric effect of the non-catalytic sites on catalysis could be detected for the activated enzyme lacking bound Pγ. The intrinsic affinity of a synthetic C-terminal (residues 63-87) Pγ peptide to bind and to inhibit the hydrolytic activity of activated PDE was enhanced 300-fold in the presence of cGMP compared with cAMP. We conclude that the binding of cGMP to the non-catalytic sites of PDE induces an allosteric change in the structure of the catalytic domain that greatly enhances the interaction of the C-terminus of Pγ with the catalytic domain.

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41

Mozaceanu, Cristina, Christopher G. P. Taylor, Jerico R. Piper, Stephen P. Argent, and Michael D. Ward. "Catalysis of an Aldol Condensation Using a Coordination Cage." Chemistry 2, no. 1 (January 25, 2020): 22–32. http://dx.doi.org/10.3390/chemistry2010004.

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The aldol condensation of indane-1,3-dione (ID) to give ‘bindone’ in water is catalysed by an M8L12 cubic coordination cage (Hw). The absolute rate of reaction is slow under weakly acidic conditions (pH 3–4), but in the absence of a catalyst it is undetectable. In water, the binding constant of ID in the cavity of Hw is ca. 2.4 (±1.2) × 103 M−1, giving a ∆G for the binding of −19.3 (±1.2) kJ mol−1. The crystal structure of the complex revealed the presence of two molecules of the guest ID stacked inside the cavity, giving a packing coefficient of 74% as well as another molecule hydrogen-bonded to the cage’s exterior surface. We suggest that the catalysis occurs due to the stabilisation of the enolate anion of ID by the 16+ surface of the cage, which also attracts molecules of neutral ID to the surface because of its hydrophobicity. The cage, therefore, brings together neutral ID and its enolate anion via two different interactions to catalyse the reaction, which—as the control experiments show—occurs at the exterior surface of the cage and not inside the cage cavity.

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42

Hu, Kuan, Meng Zhao, Tianlong Zhang, Manwu Zha, Chen Zhong, Yu Jiang, and Jianping Ding. "Structures of trans-2-enoyl-CoA reductases from Clostridium acetobutylicum and Treponema denticola: insights into the substrate specificity and the catalytic mechanism." Biochemical Journal 449, no. 1 (December 7, 2012): 79–89. http://dx.doi.org/10.1042/bj20120871.

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TERs (trans-2-enoyl-CoA reductases; EC 1.3.1.44), which specifically catalyse the reduction of crotonyl-CoA to butyryl-CoA using NADH as cofactor, have recently been applied in the design of robust synthetic pathways to produce butan-1-ol as a biofuel. We report in the present paper the characterization of a CaTER (a TER homologue in Clostridium acetobutylicum), the structures of CaTER in apo form and in complexes with NADH and NAD+, and the structure of TdTER (Treponema denticola TER) in complex with NAD+. Structural and sequence comparisons show that CaTER and TdTER share approximately 45% overall sequence identity and high structural similarities with the FabV class enoyl-acyl carrier protein reductases in the bacterial fatty acid synthesis pathway, suggesting that both types of enzymes belong to the same family. CaTER and TdTER function as monomers and consist of a cofactor-binding domain and a substrate-binding domain with the catalytic active site located at the interface of the two domains. Structural analyses of CaTER together with mutagenesis and biochemical data indicate that the conserved Glu75 determines the cofactor specificity, and the conserved Tyr225, Tyr235 and Lys244 play critical roles in catalysis. Upon cofactor binding, the substrate-binding loop changes from an open conformation to a closed conformation, narrowing a hydrophobic channel to the catalytic site. A modelling study shows that the hydrophobic channel is optimal in both width and length for the binding of crotonyl-CoA. These results provide molecular bases for the high substrate specificity and the catalytic mechanism of TERs.

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43

Smith, Andrew T., and Nigel C. Veitch. "Substrate binding and catalysis in heme peroxidases." Current Opinion in Chemical Biology 2, no. 2 (April 1998): 269–78. http://dx.doi.org/10.1016/s1367-5931(98)80069-0.

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44

Dorel, Ruth, and Ben L. Feringa. "Stereodivergent Anion Binding Catalysis with Molecular Motors." Angewandte Chemie 132, no. 2 (December 12, 2019): 795–99. http://dx.doi.org/10.1002/ange.201913054.

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45

Gerola, Adriana P., Paulo F. A. Costa, Frank H. Quina, Haidi D. Fiedler, and Faruk Nome. "Zwitterionic surfactants in ion binding and catalysis." Current Opinion in Colloid & Interface Science 32 (November 2017): 39–47. http://dx.doi.org/10.1016/j.cocis.2017.10.002.

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46

Dorel, Ruth, and Ben L. Feringa. "Stereodivergent Anion Binding Catalysis with Molecular Motors." Angewandte Chemie International Edition 59, no. 2 (January 7, 2020): 785–89. http://dx.doi.org/10.1002/anie.201913054.

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47

SOLANO, Francisco, Celia JIMÉNEZ-CERVANTES, José H. MARTÍNEZ-LIARTE, José C. GARCÍA-BORRÓN, José R. JARA, and José A. LOZANO. "Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome tautomerase." Biochemical Journal 313, no. 2 (January 15, 1996): 447–53. http://dx.doi.org/10.1042/bj3130447.

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Dopachrome tautomerase (DCT; EC 5.3.3.12) catalyses the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid in the mammalian eumelanogenic biosynthetic pathway. This enzyme, also named TRP2, belongs to a family of three metalloenzymes termed the tyrosinase-related proteins (TRPs). It is well known that tyrosinase has copper in its active site. However, the nature of the metal ion in the active site of DCT is under discussion. Whereas theoretical predictions based on similarity between the protein sequences of the TRPs suggest the presence of copper, the different inhibition pattern of DCT with some metal chelators compared with that of tyrosinase suggests that the nature of the metal ion could differ. Direct estimations of the metal content in purified DCT preparations show the presence of around 1.5 Zn atoms/molecule and the absence of copper. Apoenzyme preparation by treatment of DCT with cyanide or o-phenanthroline followed by reconstitution experiments of tautomerase activity in the presence of different ions confirmed that the metal cofactor for the DCT active site is zinc. Our results are consistent with Zn2+ chelation by the highly conserved histidine residues homologous to the histidines at the classical copper-binding sites in tyrosinase. This finding accounts for the reaction catalysed by DCT, i.e. a tautomerization, versus the copper-mediated oxidations catalysed by tyrosinase. Based on the predicted tetrahedrical co-ordination of the zinc ions in the enzyme active site, a molecular mechanism for the catalysis of L-dopachrome tautomerization is proposed. From the present data, the existence of additional ligands for metal ions other than zinc in the DCT molecule, such as the proposed cysteine iron-binding sites, cannot be completely ruled out. However, if such sites exist, they could be subsidiary binding sites, whose function would be likely to stabilize the protein.

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Szedlacsek, S. E., R. G. Duggleby, and M. O. Vlad. "Enzyme catalysis as a chain reaction." Biochemical Journal 279, no. 3 (November 1, 1991): 855–61. http://dx.doi.org/10.1042/bj2790855.

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A new type of enzyme kinetic mechanism is suggested by which catalysis may be viewed as a chain reaction. A simple type of one-substrate/one-product reaction mechanism has been analysed from this point of view, and the kinetics, in both the transient and the steady-state phases, has been reconsidered. This analysis, as well as literature data and theoretical considerations, shows that the proposed model is a generalization of the classical ones. As a consequence of the suggested mechanism, the expressions, and in some cases even the significance of classical constants (Km and Vmax.), are altered. Moreover, this mechanism suggests that, between two successive enzyme-binding steps, more than one catalytic act could be accomplished. The reaction catalysed by alcohol dehydrogenase was analysed, and it was shown that this chain-reaction mechanism has a real contribution to the catalytic process, which could become exclusive under particular conditions. Similarly, the mechanism of glycogen phosphorylase is considered, and two partly modified versions of the classical mechanism are proposed. They account for both the existing experimental facts and suggest the possibility of chain-reaction pathways for any polymerase.

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Krishna, Siddarth H., Casey B. Jones, and Rajamani Gounder. "Dynamic Interconversion of Metal Active Site Ensembles in Zeolite Catalysis." Annual Review of Chemical and Biomolecular Engineering 12, no. 1 (June 7, 2021): 115–36. http://dx.doi.org/10.1146/annurev-chembioeng-092120-010920.

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Catalysis science is founded on understanding the structure, number, and reactivity of active sites. Kinetic models that consider active sites to be static and noninteracting entities are routinely successful in describing the behavior of heterogeneous catalysts. Yet, active site ensembles often restructure in response to their external environment and even during steady-state catalytic turnover, sometimes requiring non-mean-field kinetic treatments to describe distance-dependent interactions among sites. Such behavior is being recognized more frequently in modern catalysis research, with the advent of experimental methods to quantify turnover rates with increasing precision, an expanding arsenal of operando characterization tools, and computational descriptions of atomic structure and motion at chemical potentials and timescales increasingly relevant to reaction conditions. This review focuses on dynamic changes to metal active site ensembles on zeolite supports, which are silica-based crystalline materials substituted with Al that generate binding sites for isolated and low-nuclearity metal site ensembles. Metal sites can become solvated and mobilized during reaction, facilitating interactions among sites that change their nuclearity and function. Such intersite communication can be regulated by the zeolite support, resulting in non-single-site and potentially non-mean-field kinetic behavior arising from mechanisms of catalytic action that combine elements of those canonically associated with homogeneous and heterogeneous catalysis.We discuss recent literature examples that document dynamic active site behavior in metal-zeolites and outline methodologies to identify and interpret such behavior. We conclude with our outlook on future research directions to develop this evolving branch of catalysis science and harness it for practical applications.

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50

Bankhead, Troy M., Bernard J. Etzel, Felise Wolven, Sylvain Bordenave, Jeffrey L. Boldt, Teresa A. Larsen, and Anca M. Segall. "Mutations at Residues 282, 286, and 293 of Phage λ Integrase Exert Pathway-Specific Effects on Synapsis and Catalysis in Recombination." Journal of Bacteriology 185, no. 8 (April 15, 2003): 2653–66. http://dx.doi.org/10.1128/jb.185.8.2653-2666.2003.

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ABSTRACT Bacteriophage λ integrase (Int) catalyzes site-specific recombination between pairs of attachment (att) sites. The att sites contain weak Int-binding sites called core-type sites that are separated by a 7-bp overlap region, where cleavage and strand exchange occur. We have characterized a number of mutant Int proteins with substitutions at positions S282 (S282A, S282F, and S282T), S286 (S286A, S286L, and S286T), and R293 (R293E, R293K, and R293Q). We investigated the core- and arm-binding properties and cooperativity of the mutant proteins, their ability to catalyze cleavage, and their ability to form and resolve Holliday junctions. Our kinetic analyses have identified synapsis as the rate-limiting step in excisive recombination. The IntS282 and IntS286 mutants show defects in synapsis in the bent-L and excisive pathways, respectively, while the IntR293 mutants exhibit synapsis defects in both the excision and bent-L pathways. The results of our study support earlier findings that the catalytic domain also serves a role in binding to core-type sites, that the core contacts made by this domain are important for both synapsis and catalysis, and that Int contacts core-type sites differently among the four recombination pathways. We speculate that these residues are important for the proper positioning of the catalytic residues involved in the recombination reaction and that their positions differ in the distinct nucleoprotein architectures formed during each pathway. Finally, we found that not all catalytic events in excision follow synapsis: the attL site probably undergoes several rounds of cleavage and ligation before it synapses and exchanges DNA with attR.

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Journal articles on the topic 'Binding and catalysis'

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