Science

Covalent Catalysis by Enzymes

Author: L.B. Spector

Publisher: Springer

ISBN:

Category: Science

Page: 276

View: 496

Some years ago one of my students and I reported that the acetate kinase reaction is mediated by a phosphorylated form of the enzyme [R. S. Anthony and L. B. Spector, lBe 245, 6739 (1970)]. The reversible reaction between ATP and acetate to give acetyl phosphate and ADP had hitherto been thought to proceed by direct transfer of a phosphoryl group from A TP to acetate in a single-displacement reaction. But now it became clear that acetate kinase was one of that substantial number of enzymes whose mech anism is that of the double displacement. For some reason, I began to wonder about the possibility that all enzymes, like acetate kinase, are double displacement enzymes, and do their work by covalent catalysis. For one thing, I could not think of a single instance of an enzyme for which single displacement catalysis had been proved, and inquiries on this point among knowledgeable friends elicited the same negative response. Moreover, it was long known that the two other kinds of chemical catalysis~homo geneous and heterogeneous~occur through the intermediary formation of a covalent bond between catalyst and reactant. I began to feel confident that chemical catalysis by enzymes must happen the same way.
Science

Covalent Catalysis by Enzymes

Author: L.B. Spector

Publisher: Springer Science & Business Media

ISBN:

Category: Science

Page: 276

View: 895

Some years ago one of my students and I reported that the acetate kinase reaction is mediated by a phosphorylated form of the enzyme [R. S. Anthony and L. B. Spector, lBe 245, 6739 (1970)]. The reversible reaction between ATP and acetate to give acetyl phosphate and ADP had hitherto been thought to proceed by direct transfer of a phosphoryl group from A TP to acetate in a single-displacement reaction. But now it became clear that acetate kinase was one of that substantial number of enzymes whose mech anism is that of the double displacement. For some reason, I began to wonder about the possibility that all enzymes, like acetate kinase, are double displacement enzymes, and do their work by covalent catalysis. For one thing, I could not think of a single instance of an enzyme for which single displacement catalysis had been proved, and inquiries on this point among knowledgeable friends elicited the same negative response. Moreover, it was long known that the two other kinds of chemical catalysis~homo geneous and heterogeneous~occur through the intermediary formation of a covalent bond between catalyst and reactant. I began to feel confident that chemical catalysis by enzymes must happen the same way.

Non-Covalent Catalysis and Hydrogen Bonding

Author: Anonym

Publisher:

ISBN:

Category:

Page: 40

View: 393

Research Paper (undergraduate) from the year 2019 in the subject Chemistry - Bio-chemistry, grade: 1,0, University of Cologne, language: English, abstract: This work is about the non-covalent catalysis and concentrates on the hydrogen-bond catalysis. Nowadays it is common to use catalysis in organic synthesis. It can help in orienting the substrates, lowering barriers to reaction and accelerating the rates of reaction. In addition to metal-ligand systems and biocatalysts, there is another class of catalysts, the organocatalysts which are free of any metals, like many enzymes. The organocatalysts often consist of chiral compounds. The output materials are easy to find in the nature. How these catalysts accelerate the reaction rates is a central question in organic synthesis. It is important to distinguish the interactions with the organic substrates between covalent and non-covalent bonds. The activation of a carbonyl compound by conversion into an enamine or into an iminium ion belongs to the covalent catalysis, while to increase the electrophilicity of a carbonyl group by formation of hydrogen bondings is a typical example for non-covalent organocatalysis. Thus, the acceleration and the control of the reaction rates depend on formation of hydrogen bonds for non-covalent organocatalysis. It is possible to catalyse two hydrogen bonds which occur in dual hydrogen bonding donors.
Science

Enzyme Catalysis and Regulation

Author: Gorden Hammes

Publisher: Elsevier

ISBN:

Category: Science

Page: 276

View: 827

Enzyme Catalysis and Regulation is an introduction to enzyme catalysis and regulation and covers topics ranging from protein structure and dynamics to steady-state enzyme kinetics, multienzyme complexes, and membrane-bound enzymes. Case studies of selected enzyme mechanisms are also presented. This book consists of 11 chapters and begins with a brief overview of enzyme structure, followed by a discussion on methods of probing enzyme structure such as X-ray crystallography and optical spectroscopy. Kinetic methods are then described, with emphasis on the general principles of steady-state and transient kinetics. The chemical principles involved in enzyme catalysis are also discussed, and case studies of a few well-documented enzymes are presented. The regulation of enzyme activity is analyzed from a nongenetic viewpoint, with particular reference to binding isotherms and models for allosterism. Two particular enzymes, aspartate transcarbamoylase and phosphofructokinase, are used as examples of well-studied regulatory enzymes. The last two chapters focus on multienzyme complexes and membrane-bound enzymes. This monograph is intended for graduate students, advanced undergraduates, and research workers in molecular biology and biochemistry.
Science

Evaluation of Enzyme Inhibitors in Drug Discovery

Author: Robert A. Copeland

Publisher: John Wiley & Sons

ISBN:

Category: Science

Page: 295

View: 185

Vital information for discovering and optimizing new drugs "Understanding the data and the experimental details that support it has always been at the heart of good science and the assumption challenging process that leads from good science to drug discovery. This book helps medicinal chemists and pharmacologists to do exactly that in the realm of enzyme inhibitors." -Paul S. Anderson, PhD This publication provides readers with a thorough understanding of enzyme-inhibitor evaluation to assist them in their efforts to discover and optimize novel drug therapies. Key topics such as competitive, noncompetitive, and uncompetitive inhibition, slow binding, tight binding, and the use of Hill coefficients to study reaction stoichiometry are all presented. Examples of key concepts are presented with an emphasis on clinical relevance and practical applications. Targeted to medicinal chemists and pharmacologists, Evaluation of Enzyme Inhibitors in Drug Discovery focuses on the questions that they need to address: * What opportunities for inhibitor interactions with enzyme targets arise from consideration of the catalytic reaction mechanism? * How are inhibitors evaluated for potency, selectivity, and mode of action? * What are the advantages and disadvantages of specific inhibition modalities with respect to efficacy in vivo? * What information do medicinal chemists and pharmacologists need from their biochemistry and enzymology colleagues to effectively pursue lead optimization? Beginning with a discussion of the advantages of enzymes as targets for drug discovery, the publication then explores the reaction mechanisms of enzyme catalysis and the types of interactions that can occur between enzymes and inhibitory molecules that lend themselves to therapeutic use. Next are discussions of mechanistic issues that must be considered when designing enzyme assays for compound library screening and for lead optimization efforts. Finally, the publication delves into special forms of inhibition that are commonly encountered in drug discovery efforts, but can be easily overlooked or misinterpreted. This publication is designed to provide students with a solid foundation in enzymology and its role in drug discovery. Medicinal chemists and pharmacologists can refer to individual chapters as specific issues arise during the course of their ongoing drug discovery efforts.
Science

ENZYMES: Catalysis, Kinetics and Mechanisms

Author: N.S. Punekar

Publisher: Springer

ISBN:

Category: Science

Page: 562

View: 580

This enzymology textbook for graduate and advanced undergraduate students covers the syllabi of most universities where this subject is regularly taught. It focuses on the synchrony between the two broad mechanistic facets of enzymology: the chemical and the kinetic, and also highlights the synergy between enzyme structure and mechanism. Designed for self-study, it explains how to plan enzyme experiments and subsequently analyze the data collected. The book is divided into five major sections: 1] Introduction to enzymes, 2] Practical aspects, 3] Kinetic Mechanisms, 4] Chemical Mechanisms, and 5] Enzymology Frontiers. Individual concepts are treated as stand-alone chapters; readers can explore any single concept with minimal cross-referencing to the rest of the book. Further, complex approaches requiring specialized techniques and involved experimentation (beyond the reach of an average laboratory) are covered in theory with suitable references to guide readers. The book provides students, researchers and academics in the broad area of biology with a sound theoretical and practical knowledge of enzymes. It also caters to those who do not have a practicing enzymologist to teach them the subject.
Science

Enzyme Kinetics: Catalysis and Control

Author: Daniel L. Purich

Publisher: Elsevier

ISBN:

Category: Science

Page: 920

View: 674

Far more than a comprehensive treatise on initial-rate and fast-reaction kinetics, this one-of-a-kind desk reference places enzyme science in the fuller context of the organic, inorganic, and physical chemical processes occurring within enzyme active sites. Drawing on 2600 references, Enzyme Kinetics: Catalysis & Control develops all the kinetic tools needed to define enzyme catalysis, spanning the entire spectrum (from the basics of chemical kinetics and practical advice on rate measurement, to the very latest work on single-molecule kinetics and mechanoenzyme force generation), while also focusing on the persuasive power of kinetic isotope effects, the design of high-potency drugs, and the behavior of regulatory enzymes. Historical analysis of kinetic principles including advanced enzyme science Provides both theoretical and practical measurements tools Coverage of single molecular kinetics Examination of force generation mechanisms Discussion of organic and inorganic enzyme reactions

Textbook Of Biochemistry

Author: Puri

Publisher: Elsevier India

ISBN:

Category:

Page: 920

View: 132

The book presents a detailed and authoritative exposition of the basic principles and applications of biochemistry. It thouroughly covers the syllabus recommended by MCI for undergraduate medical students. It focuses primarily on the fundamental concepts and explain them in detail. Numerous line diagrams, in an attractive two-colour format, are provided to illustrate the concepts and help the students in grasping their significance. Medical applications of biochemistry are discussed through extended examples and clinical cases. About the Author : - Dinesh Puri, Professor, Dept. of Biochemistry, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi.
Science

Organic Chemistry of Enzyme-Catalyzed Reactions, Revised Edition

Author: Richard B. Silverman

Publisher: Elsevier

ISBN:

Category: Science

Page: 800

View: 614

The Organic Chemistry of Enzyme-Catalyzed Reactions is not a book on enzymes, but rather a book on the general mechanisms involved in chemical reactions involving enzymes. An enzyme is a protein molecule in a plant or animal that causes specific reactions without itself being permanently altered or destroyed. This is a revised edition of a very successful book, which appeals to both academic and industrial markets. Illustrates the organic mechanism associated with each enzyme-catalyzed reaction Makes the connection between organic reaction mechanisms and enzyme mechanisms Compiles the latest information about molecular mechanisms of enzyme reactions Accompanied by clearly drawn structures, schemes, and figures Includes an extensive bibliography on enzyme mechanisms covering the last 30 years Explains how enzymes can accelerate the rates of chemical reactions with high specificity Provides approaches to the design of inhibitors of enzyme-catalyzed reactions Categorizes the cofactors that are appropriate for catalyzing different classes of reactions Shows how chemical enzyme models are used for mechanistic studies Describes catalytic antibody design and mechanism Includes problem sets and solutions for each chapter Written in an informal and didactic style