[PDF] Studies On The Role Of Conformation In Enzyme Catalysis And Control eBook

Author : Judith Klinman
Publisher : Springer
Page : 217 pages
File Size : 40,81 MB
Release : 2013-09-14
Category : Science
ISBN : 3642389627

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Christopher M. Cheatum and Amnon Kohen, Relationship of Femtosecond–Picosecond Dynamics to Enzyme-Catalyzed H-Transfer. Cindy Schulenburg and Donald Hilvert, Protein Conformational Disorder and Enzyme Catalysis. A. Joshua Wand, Veronica R. Moorman and Kyle W. Harpole, A Surprising Role for Conformational Entropy in Protein Function. Travis P. Schrank, James O. Wrabl and Vincent J. Hilser, Conformational Heterogeneity Within the LID Domain Mediates Substrate Binding to Escherichia coli Adenylate Kinase: Function Follows Fluctuations. Buyong Ma and Ruth Nussinov, Structured Crowding and Its Effects on Enzyme Catalysis. Michael D. Daily, Haibo Yu, George N. Phillips Jr and Qiang Cui, Allosteric Activation Transitions in Enzymes and Biomolecular Motors: Insights from Atomistic and Coarse-Grained Simulations. Karunesh Arora and Charles L. Brooks III, Multiple Intermediates, Diverse Conformations, and Cooperative Conformational Changes Underlie the Catalytic Hydride Transfer Reaction of Dihydrofolate Reductase. Steven D. Schwartz, Protein Dynamics and the Enzymatic Reaction Coordinate.

Author : Marlene Deluca
Publisher : Elsevier
Page : 536 pages
File Size : 19,49 MB
Release : 2014-06-28
Category : Science
ISBN : 148321723X

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Current Topics in Cellular Regulation: Volume 24, Enzyme Catalysis and Control is a compendium of papers that discusses phosphoryl transfer reactions, the role of water on the free energy of hydrolysis of pyrophosphate, and the hormonal actions of vitamin D. Other papers describe the regulation lipid metabolism by a lipid-carrying protein, the GABA, and taurine enzymes in mammalian brain. One paper examines the role of vitamin D in the metabolism of cells, as well as in the whole animal. Upon absorption in the body, the vitamin undergoes various metabolic transformations before interacting with specific receptors, and then inducting the genome in the target tissues to generate biological and hormonal responses. Another paper notes the possibility of a genetic defect in cancer cells that results in the abnormal accumulation of sterol carrier protein (SCP) and cholesterol in vivo; and also in the inability to maintain levels of SCP or cholesterol in vitro. One paper shows that tartrate, or other organic acids, secreted into the medium by the penicillia keeps the pH in an optimal range for acid protease degradation of proteins and glycoproteins. This mechanism helps the fungus to survive in a nutrient environment (which is unbalanced with respect to an optimum C/N ratio and at a pH unfavorable to many bacteria and other life forms). Another paper proposes a model for the modulation of ATP synthetase activities and medium exchange reactions by energy input, substrate concentration, or others that affect the microenvironment of the enzyme under certain conditions. The compendium will prove beneficial to molecular biologists, general biologists, microbiologists, and biochemists.

Author : Bryant M. Wood
Publisher :
Page : pages
File Size : 31,80 MB
Release : 2011
Category :
ISBN :

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The focus of this research is the role of conformational flexibility in catalysis by a TIM-barrel enzyme in pyrimidine biosynthesis, orotidine 50́9-monophosphate decarboxylase (OMPDC). OMPDC catalyzes the decarboxylation of OMP to UMP; the uncatalyzed rate for this reaction has been estimated to be 2.8 x 1016 s-1 (1). The slow rate without OMPDC is attributable to the lack of internal stabilization of the negative charge which must develop in the intermediate after decarboxylation. Because OMPDC does not utilize a cofactor in its mechanism, discovering how it is able to enhance this very slow rate to near the limits of diffusion is an important problem, kcat/KM = 1.3 x 107 M-1s-1 (2). Through alanine-scanning mutagenesis, I have identified important residues in OMPDC catalysis (3, 4). The large impact of mutating residues on the periphery of the active-site has helped develop an understanding of the importance of conformational change. Residues Ser127 and Gln185 from two different loops form an interaction that helps to coordinate loop closure with substrate binding; these residues also interact with the substrate (4). Besides active-site loop closure, crystal structures reveal the TIM-barrel of OMPDC to function as two halves which move toward one another when ligand binds. Near one of the boundaries between these two domains, I identified residues remote from the active-site which form a hydrophobic cluster in the 0́−closed0́+ state of the enzyme; Val182 from the mobile active-site loop becomes anchored in this cluster upon loop closure (3). Through site-directed mutagenesis, enzyme assays, and collaboration with X-ray crystallography experts in the Almo Group at Columbia University, I was able to determine that these hydrophobic interactions were important specifically to conformational change from an 0́−open0́+ to a 0́−closed0́+ state of the enzyme and that mutations to these residues had little impact on the 0́−closed0́+ state itself (3). It is thought that this cluster helps to coordinate the movement of domains as well as stabilize loop closure when substrate binds. Additional residues at the opposite domain interface are currently being investigated. In order to determine the rate-limiting step and to gain a better picture of the energy landscape for OMPDC catalysis, I measured the dependence of the kinetic parameters for various OMPDCs on viscosity (2). This allowed me to determine to what degree chemistry was important to the measured rate because changing viscosity affects the rate of physical steps outside of the active-site while leaving unchanged the chemical steps secluded from solvent by the active-site. For kcat and kcat/KM for yeast OMPDC and kcat/KM for the archaeal M. thermautorophicus OMPDC, OMP decarboxylation was found to be only partially dependent on the rate of chemical steps in the enzyme (2). Therefore, the rate of carbon-carbon bond cleavage, which occurs ca. 2.8 x 10-16 s-1 in solution, is enhanced by OMPDC near to the rate at which substrate can diffuse into the active site. Furthermore, kcat/KM for a 0́−faster0́+ substrate, 5-fluoroOMP (FOMP), was found to be completely dependent on viscosity for the archaeal enzyme. This demonstrated that the rate of FOMP decarboxylation is limited by the rate of FOMP diffusing into the active site. This allowed for an explanation of the small difference in the kcat/KM for OMP and FOMP, 2-fold as opposed to 1000-fold as predicted. Also, evidence for slow conformational change upon substrate binding was gleaned from the inability for FOMP decarboxylation catalyzed by the yeast enzyme to reach complete dependence on solvent viscosity. In short, because the chemical rate is far too fast and because diffusive processes will exhibit linear dependence on viscosity, there must be a viscosity sensitive conformational change in the yeast enzyme. By applying the tools of enzymology learned in the Gerlt Laboratory and working successfully with numerous collaborators, I have furthered our understanding of the mechanism of one of Nature0́9s best catalysts, OMPDC. Increasingly in enzymology, the role of conformational change in enzyme catalysis has been recognized as an important one. This research has shed light on the conformational changes that take place when substrate binds OMPDC and how the two events are coordinated.

Author : Athel Cornish-Bowden
Publisher : Elsevier
Page : 221 pages
File Size : 22,84 MB
Release : 2014-05-20
Category : Science
ISBN : 1483164675

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Principles of Enzyme Kinetics discusses the principles of enzyme kinetics at an intermediate level. It is primarily written for first-year research students in enzyme kinetics. The book is composed of 10 chapters. Chapter 1 provides the basic principles of enzyme kinetics with a brief discussion of dimensional analysis. Subsequent chapters cover topics on the essential characteristics of steady-state kinetics, temperature dependence, methods for deriving steady-state rate equations, and control of enzyme activity. Integrated rate equations, and introductions to the study of fast reactions and the statistical aspects of enzyme kinetics are provided as well. Chemists and biochemists will find the book invaluable.

Author : Xiaoyu Wang
Publisher : Springer
Page : 134 pages
File Size : 17,57 MB
Release : 2016-07-27
Category : Technology & Engineering
ISBN : 3662530686

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This book describes the fundamental concepts, the latest developments and the outlook of the field of nanozymes (i.e., the catalytic nanomaterials with enzymatic characteristics). As one of today’s most exciting fields, nanozyme research lies at the interface of chemistry, biology, materials science and nanotechnology. Each of the book’s six chapters explores advances in nanozymes. Following an introduction to the rise of nanozymes research in the course of research on natural enzymes and artificial enzymes in Chapter 1, Chapters 2 through 5 discuss different nanomaterials used to mimic various natural enzymes, from carbon-based and metal-based nanomaterials to metal oxide-based nanomaterials and other nanomaterials. In each of these chapters, the nanomaterials’ enzyme mimetic activities, catalytic mechanisms and key applications are covered. In closing, Chapter 6 addresses the current challenges and outlines further directions for nanozymes. Presenting extensive information on nanozymes and supplemented with a wealth of color illustrations and tables, the book offers an ideal guide for readers from disparate areas, including analytical chemistry, materials science, nanoscience and nanotechnology, biomedical and clinical engineering, environmental science and engineering, green chemistry, and novel catalysis.