The Enzyme Reference A Connprehensive Guidebook to Enzynne Nonnenclature, Reactions, and Methods This Page Intentionally Left Blank The Enzyme Reference A Connprehensive Guidebook to Enzynne Nonnenclature, Reactions, and Methods Daniel L. Purich R. Donald Allison Department of Biochemistry and Molecular Biology University of Florida College of Medicine Gainesville, Florida /^ ACADEMIC PRESS V—y An imprint of Elsevier Science Amsterdam Boston London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo This book is printed on acid-free paper, w Copyright © 2002, Elsevier Science (USA). All Rights Reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Academic Press, 6277 Sea Harbor Drive, Orlando, Rorida 32887-6777 Academic Press An imprint of Elsevier Science. 525 B Street, Suite 1900, San Diego, California 92101-4495, USA http://www.academicpress.com Academic Press 84 Theobald's Road, London WCIX 8RR, UK http ://w WW. academicpress. com Library of Congress Catalog Card Number: 2002113737 hitemational Standard Book Number: 0-12-568041-4 PRINTED IN THE UNITED STATES OF AMERICA 02 03 04 05 06 07 9 8 7 6 5 4 3 2 1 Table of Contents Preface vii Nonstandard Journal Abbreviations Used ix Enzyme Reference I Index 875 The Enzyme Reference: A Comprehensive Guidebook to Enzyme Nomenclature, Reactions, and Methods This Page Intentionally Left Blank Preface F ew would quarrel with the assertion that the extra- reactions classified by the Enzyme Commission, as of ordinary catalytic power of enzymes is rivaled only January of 2002, as well as many presently unclassified by their vast diversity of reaction types and their abil- enzymes for which we found sufficient documentation ity to surprise and fascinate molecular Ufe scientists and regarding their substrates, products, and reaction stoi- chemists alike. Contrary to predictions of a waning inter- chiometry. We also included many alternative enzyme est in intermediary metabolism, new enzymes continue names, while ignoring those deemed to be arcane, aban- to be discovered, especially in the fields of cell biology doned, or obviously incorrect. This compendium lists over and neuroscience. Attesting to the vibrancy of modem 6500 different enzyme-catalyzed reactions, often citing the enzyme research are the widely heralded recent discov- original paper describing a particular enzyme and/or sev- eries of ribozymes, telomerases, proteasomes, NAD+- eral authoritative reviews. When two different enzymes dependent histone deacetylases, as well as hundreds of catalyze virtually identical or very similar reactions, we new proteases, protein kinases, and an ever-growing list of have attempted to include key distinguishing features, energases that includes novel molecular motors, ion/solute along with an italicized phrase directing the reader's atten- pumps, protein-folding chaperonins, and GTP-regulatory tion to related enzyme-catalyzed reactions. We avoided enzymes. One may even view the field of cell biology distinctions made solely on a quantitative basis, because as a form of structural metabolism wherein the cell's the identical reaction in different tissues and organisms is supramolecular components are formed, remodeled, and catalyzed by enzymes with different Michaelis constants, degraded enzymatically. As more details emerge about turnover numbers, molecular weights, etc. We also made the chemical foundations of cell biology, various pro- a special effort to include reactions facilitated by plant cesses (e.g., membrane targeting, cell crawling, and cell enzymes, not only because these reactions tend to be over- division) are all taking on the appearance of biochem- looked, but because their reactions are both surprisingly ical pathways akin to those so frequently illustrated in complex and wonderfully fascinating. We also included the metabolic pathway charts. Enzymes also remain as the structures of nearly one thousand metabolites and cof actors principal targets for designing therapeutic agents-—witness to inform the reader about the chemical transformations the burgeoning fist of new inhibitors of angiotensinogen- occurring in many reactions. converting enzymes, nitric oxide synthases, cyclooxyge- nases, and cholesterogenic enzymes. Given that entire Throughout the course of this effort, we were nagged genomes have been sequenced and that powerful com- by the question: How should we handle those ATPase binatoric and array technologies have been perfected and GTPase reactions which, when written without ref- for detecting and quantifying enzyme interactions with erence to their noncovalent substratelike and product- substrates and inhibitors, expedited discovery of novel like conformational states, are currently misclassified as drugs and enzyme-based/directed therapies is especially hydrolases? This problem arises from the Enzyme Com- likely. mission's long-standing practice of describing enzyme reactions strictly in terms of transformations in covalent Such considerations underscore the need for a single- bonds. For example, myosin is classified as a hydrolase volume reference offering molecular life scientists the despite its catalysis of a force-generating contraction {e.g., name, class, EC number, reaction, essential cofactor(s), Myosinposition-i + ATP = Myosinposition-2 + ADP + Pi, and other details about each of the enzyme-catalyzed where Position-1 and Position-2 indicated the myosin's The Enzyme Reference: A Comprehensive Guidebook to Enzyme Nomenclature, Reactions, and Methods VII advancement along an actin filament). Thus, while the properties for some 600 enzymes widely used in kinetic essence of myosin's function is the making and breaking of investigations. We now extend this practice by includ- noncovalent bonds, the Enzyme Commission ignores such ing these and similar citations for thousands of enzymes transformations when classifying and naming enzymes. listed in the Enzyme Reference. Thus, while there are In truth, biological catalysis need not be attended by internet-accessible databases on enzyme-catalyzed reac- any change in covalency, leading to the recent sugges- tions, none provides such extensive and convenient access tion that an enzyme be redefined as a biological cat- to Methods in Enzymology. alyst that accelerates the making/breaking of chemical bonds [Trends in Biochemical Sciences (2001) 26, 417]. Sharing an enduring fascination about the diversity of This new definition builds on Pauling's assertion in enzyme catalysis, we have consulted thousands of origi- The Nature of the Chemical Bond that any long-lived, nal research papers and reviews, not to mention countless chemically distinct interaction constitutes a chemical abstracts, during the preparation of the Enzyme Reference. bond. These considerations point to the need for a new On many occasions, we questioned the wisdom of ever enzyme class that would include ATPases and GTPases undertaking this task, and we often remarked that our as specialized enzymes designed to transduce covalent parents were probably most responsible for our stubborn bond energy into mechanical work. (See text entry enti- pursuit of the scholarship needed to complete the project. tled "Energases.") Even so, until inconsistencies in With an abiding reverence for their values, we dedicate this classifying so-called "ATPase" and "GTPase" reactions reference book to our parents, Violet and Edward Purich are resolved, the Enzyme Reference retains the current and Edna and Robert Allison. Enzyme Commission name, classification, and numbering system for these reactions. We hope our readers will find the Enzyme Reference to be a trusted desk companion, always kept within reach. We The origins of the Enzyme Reference are rooted in painstakingly sought to achieve accuracy, and we would the Handbook of Biochemical Kinetics, which we wrote deeply appreciate reader comments, especially concern- several years ago to assist molecular life scientists ing required amendments and corrections. We would also in the design, execution, and evaluation of kinetic welcome suggestions about new enzymes that should be experiments. Because one of us (D.L.P.) has edited included in later editions. Methods in Enzymology volumes for nearly 25 years, we obtained permission to include within that handbook thou- Daniel L. Purich sands of brief citations to Methods in Enzymology arti- cles describing the preparation, assay, storage, and other R. Donald Allison VIII The Enzyme Reference: A Comprehensive Guidebook to Enzyme Nomenclature, Reactions, and Methods Nonstandard Journal Abbreviations Used ABB Archives of Biochemistry and Biophysics AE Advances in Enzymology (book series) BB A Biochimica et Biophysica Acta BBRC Biochemistry & Biophysics Research Communications BJ Biochemical Journal CBC Comprehensive Biological Catalysis (book) EJB European Journal of Biochemistry JACS Journal of the American Chemical Society JBC Journal of Biological Chemistry MIE Methods in Enzymology (book series) NAR Nucleic Acids Research PNAS Proceedings of the National Academy of Sciences, U.S.A. TiBS Trends in Biochemical Sciences The Enzyme Reference: A Comprehensive Guidebook to Enzyme Nomenclature, Reactions, and Methods ix