Encyclopedia of Molecular Biology

4899 Pages·1999·52.516 MB·English

by  Thomas E. Creighton

ENCYCLOPEDIA OF
MOLECULAR
BIOLOGY
VOLUMES 1 - 4
European' Molecular Biology Laboratory
London, England
A Wiley-lnterscience Publication
John Wiley & Sons, Inc.
New York / Chichester / Weinheim / Brisbane / Singapore / Toronto
This book is printed on acid-free paper. (@
Copyright @ 1999 by John Wiley & Sons, Inc.
All rights reserved. Published simultaneously in Canada.
No part of this publication may be reproduced, stored in a retrieval system or transmitted
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Library of Congress Cataloging-in-Publication Data:
Creighton, Thomas E., 1940-
The encyclopedia of molecular biology I Thomas E. Creighton.
p. cm.
Includes index.
ISBN 0-471-15302-8 (alk. paper)
I. Molecular biology-Encyclopedias. I. Title.
QH506.C74 1999 99-11575
572.8'03-dc21 CIP
Printed in the United States of America.
10 9 8 7 6 5 4 3 2 1
PREFACE
The Wiley Biotechnology Encyclopedias, composed of the Ency- spectrometerc, oupledw ith a knowledgeo f all protein sequences
clopedia of Molecular Biology, the Encyclopedia of Bioprocess that can be derived from the completeg enomics equenceo f the
Technology: Fermentation, Biocatalysis, and Bioseparation, organism, will serve as a powerful tool for identifying all the
the Encyclopedia of Cell Technology, and the Encyclopedia of componentso f complexm olecularm achines.
Ethical, Legal, and Policy Issues in Biotechnology, cover very The third type of biological information arises from com-
broadly four major contemporary themes in biotechnology. plex biological systemsa nd networks. Systemsi nformation is
The series comes at a fascinating time in that as we move into four-dimensionalb ecauseit varies with time. For example,t he
the twenty-first century, the discipline of biotechnology is human brain has 1012 neurons making approximately 1015
connections. From this network arises systems properties
undergoing striking paradigm changes.
Biotechnology is now beginning to be viewed as an i~- such a memory, consciousnessa, nd the ability to learn. The
formational ~.clence. In a simplistic sense, there are three important point is that systems properties cannot be under-
types of biological information. First, there is the digital or stoodf rom studying the network elements( eg,n eurons)o ne at
linear inf9rmation of our chromosomes and genes, with the a time; rather, the collectiveb ehavior of the elementsn eedst o
four-letter alphabet composed of G, C, A, and T (the bases be studied together. To study most biological systems,t hree
Guanine, Cytosine, Adenine, and Thymine). Variation in the issues need to be stressed.F irst, most biological systemsa re
order of these letters in the digital strings of our chromosomes too complext o study directly; therefore they must be divided
or our expressed genes (or mRNAs) generates information into tractable subsystemsw hose properties in part reflect
of several distinct types: genes, regulatory machinery, and those of the system. These subsystemsm ust be sufficiently
information that enables chromosomes to carry out their tasks small to analyze all their elementsa nd connections.S econd,
as informational organelles (eg, centromeric and telomeric high-throughput analytic or global tools are required for study-
ing many systems elements at one time (seeb elow). Finally,
sequences).
Second, there is the three-dimensional information of the systemsi nformation needst o be modeledm athematically
proteins, the molecular machines of life. Proteins are strings before systems properties can be predicted and ultimately
of amino acids employing a 20-letter alphabet. Proteins pose understood. This will require recruiting computer scientists
four technical challenges: (i) Proteins are synthesized as linear and applied mathematicsi nto biology-just as the attempts to
strings and fold into precise three-dimensional structures as deciphert he information of completeg enomesa nd the protein
dictated by the order of amino acid residues in the string. Can folding and structure/function problems have required the
we formulate the rules for protein folding to predict three- recruitment of comput~tionals cientists.
dimensional structure from primary amino acid sequence?T he I would be remiss not to point out that there are many other
identification and comparative analysis of all human and model moleculest hat generateb iological information-amino acids,
organism (bacteria, yeast, nematode, fly, mouse, etc.) genes carbohydrates,l ipids, etc. These too must be studied in the
and proteins will eventually lead to a lexicon of motifs that are contexto f their specific structures and specificf unctions.
the building block components of genes and proteins. These The deciphering and manipulation of thesev arious types of
motifs will greatly constrain the shape space computational al- biological information represent an enormoust echnical chal-
gorithms must search to successfully correlate primary amino lenge for biotechnology.Y et major new and powerful tools for
acid sequence with the correct three-dimensional shapes. The doing so are emerging.
protein-folding problem will probably be solved within the One class of tools for deciphering biological information is
next 10 to 15 years. (ii) Can we predict protein function from termed high-throughput analytic or global tools. These tools
knowledge of the three-dimensional structure? Once again the can study many genes or chromosomef eatures (genomics),
lexicon of motifs with their functional as well as structural many proteins (proteomics),o r many cells rapidly: large-scale
correlations will playa critical role in solving this problem. (iii) DNA sequencing; genome-wideg enetic mapping; cDNA or
How do the myriad of chemical modifications of proteins (eg, oligonucleotidea rrays; two-dimensionalg el electrophoresisa nd
phosphorylation, acetylation) alter their structures and modify other global protein separationt echnologies;m asss pectromet-
their functions? The mass spectrometer will playa key role ric analysiso f proteins and protein fragments;m ultiparameter,
in identifying secondary modifications. (iv) How do proteins high-throughput cell and chromosome sorting; and high-
interact with one another and/or with other macromolecules throughput phenotypica ssays.
to form complex molecular machines (eg, the ribosomal sub- A seconda pproacht o the deciphering and manipulation of
units)? If these functional complexes can be isolated, the mass biological information centers around combinatorial strate-
gies. The basic idea is to synthesizea n informational string Biotechnology and its applications raise a host of social, eth-
(DNA fragments,R NA fragments,p rotein fragments, antibody ical, and legal questions; for example, genetic privacy, germline
combinings ites, etc.) using all combinationso f the basicl etters genetic engineering, cloning animals, genes that influence
of the correspondinga lphabet-thus creating many different behavior, cost of therapeutic drugs generated by biotechnol-
shapest hat can be usedt o activate, inhibit, or complementt he ogy, animal rights, and the nature and control of intellectual
biological functions of designated three-dimensional shapes property.
(eg,a moleculei n a signal transduction pathway). The powero f The challenge clearly is to educate society so that each cit-
combinationalc hemistry is just beginning to be appreciated. izen can thoughtfully and rationally deal with these issues,
A critical approach to deciphering biological information for ultimately society dictates the resources and regulations
will ultimately be the ability to visualize the functioning of that circumscribe the development and practice of biotechnol-
genes,p roteins, cells, and other informational elementsw ithin ogy. mtimately, I feel enormous responsibility rests with sci-
living organisms( in vivo informational imaging). entists to inform and educate society about the challenges as
Finally, there are the computational tools required to col- well as the opportunities arising from biotechnology. These
lect, store, analyze,m odel, and ultimately distribute the var- are critical issues for biotechnology that are developed in de-
ious types of biological information. The creation presents a tail in the Encyclopedia of Ethical, Legal, and Policy ]ssues in
challengec omparablet o that of developingo f new instrumen- Biotechnology.
tation and new chemistries. Once again, this means recruit- The view that biotechnology is an informational science
ing computers cientistsa nd applied mathematicianst o biology. pervades virtually every aspect of this science-including
The biggest challengei n this regard is the language barriers discovery, reduction to practice, and societal concerns. These
that separated ifferent scientific disciplines.T eachingb iology Encyclopedias of Biotechnology reinforce the emerging in-
as an informational scienceh as beena very effectivem eansf or formational paradigm change that is powerfully positioning
breechingt hesel anguageb arriers. science as we move into the twenty-first century to more
The challengei s, of course,t o deciphert hese various types effectively decipher and manipulate for humankind's benefit
of biological information and then be able to use this infor- the biological information of relevant living organisms.
mation to manipulate genes,p roteins, cells, and informational
pathways in living organismst o eliminate or prevent disease,
produceh igher yield crops,o r increaset he productivity of ani- LEROYH OOD
mal productsa nd meat. UniversityofWashington
CONTRIBUTORS
Hanna E. Abboud, University of Texas, Health Science Center, San Antonio, F. Bonomi, Universita Degli Studi Di Milano, Milano, Italy
TX Ralph A. Bradshaw, University of California, Irvine, CA
Sankar Adhya, National Cancer Institute, National Institutes of Health, Bertram Brenig, Georg-August University, Gottingen, Germany
Bethesda, MD Kenneth J. Breslauer, Rutgers University, Piscataway, NJ
Hiroji Aiba, Nagoya University, Chikusa, Nagoya, Japan Roy J. Britten, California Institute of Technology, Corona del Mar, CA
Philip Aisen, Albert Einstein College of Medicine, Bronx, NY Maurizio Brunori, University of Rome, "La Sapienza, " Rome, Italy
Rudolf K. Allemann, University of Birmingham, Birmingham, United Bernd Bukau, Albert-Ludwigs Universitat Freiburg, Freiburg, Germany
Kingdom Jens R. Bundgaard, University of Copenhagen, Copenhagen, Denmark
Nicholas Allen, The Babraham Institute, Cambridge, United Kingdom Arsene Burny, Universite Libre de Bruxelles, Rhode Saint Genese, Belgium
Suresh Ambudkar, National Cancer Institute, National Institutes of Health, Kenneth Burtis, University of California, Davis, CA
Bethesda, MD
Ana Busturia, Universidad Aut noma de Madrid, Madrid, Spain
Vernon E. Anderson, Case Western Reserve University, Cleveland, OH Giulio L. Cantoni, NIMH, National Institutes of Health, Bethesda, Ma
Berlil Andersson, Stockholm University, Stockholm, Sweden M. Stella Carlomango, Universita Degli Studi Di Napoli Federico II, Napoli,
Ruth Hogue Angeletti, Albert Einstein College of Medicine, Bronx, NY
Italy
Rodolfo Aramayo, schering-Plough Research Institute, Kenilworth, NJ Gerald M. Carlson, University of Missouri, Kansas City, MO
Yari Argon, University of Chicago, Chicago, IL Graham Carpenter, Vanderbilt University, Nashville, TN
K. Arora, University of California, Irvine, CA Robin W. Carrell, University of Cambridge, Cambridge, United Kingdom
leonie K. Ashman, Hanson Center for Cancer Research, Adeleide, Australia James Castelli-Gair, University of Cambridge, Cambridge, United Kingdom
John F. Atkins, University of Utah, Salt Lake City, UT Enrique Cerda-Olmedo, Universidad de Sevilla, Sevilla, Spain
William M. Atkins, University of Washington, Seattle, WA Jonathan Chaires, University of Mississippi Medical Center, Jackson, MS
Daniel Atkinson, UCLA, Los Angeles, CA Kung-Yao Chang, MRC Laboratory of Molecular Biology, Cambridge,
David Auld, Harvard Medical School, Boston, MA United Kingdom
Paul Babitzke, Pennsylvania State University, University Park, PA Lee Chao, Medical University of South Carolina, Charleston, SC
Andrew Baird, Prizm Pharmaceuticals, San Diego, CA Ansuman Chattopadhyay, Vanderbilt University School of Medicine,
Stacey JoB aker, Temple University School of Medicine, Philadelphia, PA Nashville, TN
Tom Baldwin, Texas A&M University, College Station, TX Walter Chazin, Scripps Research Institute, La Jolla, CA
Michael Bamshad, University of Utah Health Sciences Center, Salt Lake Elizabeth H. Chen, University of Texas, Southwestern Medical Center,
City, UT Dallas, TX
Probal Banerjee, College of Staten Island, New York, NY Donald P. Cheney, Northeastern University, Boston, MA
Ruma Banerjee, University of Nebraska, Lincoln, NE Andreas Chrambach, National Institutes of Health, Bethesda, Ma
William Ro Bauer, University of California, San Francisco, CA Jason Christiansen, Virginia Polytechnic Institute, Blacksburg, VA
Christopher Baum, Heinrich-Pette Institut, Hamburg, Germany Jon A. Christopher, Texas A&M University, College Station, TX
Edward A. Bayer, Weizmann Institute of Science, Rehovot, Israel Brian F. C. Clark, Aarhus University, Aarhus, Denmark
Miguel Beato, Philipps-Universitaet Marburg, Institut fuer Molekularbiolo- Dennis Clegg, University of California, Santa Barbara, CA
gie, Marburg, Germany F. Cliften, University of Colorado Health Sciences Center, Denver, CO
Dorothy Beckett, University of Maryland, Baltimore, MD Georges N. Cohen, Institut Pasteur, Paris, France
Samuel Benchimol, University of Toronto, Toronto, Ontario, Canada Roberta Colman, University of Delaware, Newark, DE
Steven Jo Benkovic, Pennsylvania State University, University Park, PA Orla M. Conneely, Baylor College of Medicine, Houston, TX
Tomas Bergman, Karolinska Institutet, Stockholm, Sweden Barry S. Cooperman, University of Pennsylvania, Philadelphia, PA
Gerald Bergtrom, University of Wisconsin, Milwaukee, WI Pamela Correll, The Pennsylvania State University, University Park, PA
Alan Bernstein, Mount Sinai Hospital, Toronto, Ontario, Canada Pascale Cossart, Institut Pasteur, Paris, France
Harris Do Bernstein, NIDDKD, National Institutes of Health, Bethesda, MD Nancy Craig, Johns Hopkins University, Baltimore, Ma
Sophie Bertrand, Universiteit Gent, Gent, Belgium Elliott Crooke, Georgetown University, Washington, DC
D. M. Bethea, Thomas Jefferson University, Philadelphia, PA Stanley T. Crooke, 1515P harmaceuticals, Inc., Carlsbad, CA
Dieter Beyer, Rhone Poulenc Rorer Recherche Developpement, Vitry-sur- Richard D. Cummings, University of Oklahoma, Oklahoma City, OK
Seine, France James Curran, Wake Forest University, Winston-Salem, NC
Timothy R. Billiar, University of Pittsburgh Medical Center, Pittsburgh, PA Michael A. Cusanovich, University of Arizona, Tucson, AZ
Asgeir Bjornsson, University of Aarhus, Aarhus, Denmark Giuseppe D'Alessio, Universita di Napoli Federico II, Napoli, Italy
Colin C. Fo Blake, Norfolk, United Kingdom Antoine Danchin, Institut Pasteur, Paris, France
vii
viii CONTRIBUTORS
P. L. Davies, Queen's University, Kingston, Ontario, Canada Herbert Geller, UMDNJ-Robert Wood Johnson Medical School,
Dennis R. Dean, Virginia Polytechnic Institute & State University, Piscataway, NJ
Blacksburg, VA John Gerig, University of California, Santa Barbara, CA
Pieter DeHaseth, Case Western Reserve University, Cleveland, OH Norman L. Gershfeld, National Institutes of Health, Bethesda, MD
Andrew J. DeMello, Imperial College, London, United Kingdom Michael Gershon, Columbia University, New York, NY
David T. Denhardt, Rutgers University, Piscataway, NJ Jonathan M. Gershoni, Tel Aviv University, Tel Aviv, Israel
W. A. Denny, University of Auckland, Auckland, New Zealand Jean-Marie Ghuysen, Universite de Liege, Liege, Belgium
Zygmunt Derewenda, University of Virginia, Charlottesville, VA Toby Gibson, European Molecular Biology Laboratory, Heidelberg,
Claude Desplan, Rockefeller University, New York, NY Germany
Raymond Devoret, Centre Universitaire, Orsay, France J. A. Girault, Chaire de Neuropharmacologie, College de France, Paris,
France
Beth Didomenico, schering-Plough Research Institute, Kenilworth, NJ
Adam Godzik, Scripps Research Institute, La Jolla, CA
Patrick DiMario, Louisiana State University, Baton Rouge, LA
Jefferey Godzik, Scripps Research Institute, La Jolla, CA
Hal B. F. Dixon, Cambridge University, Cambridge, United Kingdom
J. Peter Gogarten, University of Connecticut, Storrs Mansfield, CT
Mark Dodson, University of Arizona, Tucson, AZ
Takashi Gojobori, National Institute of Genetics, Shizuoka, Japan
Jan Drenth, Laboratory of Biophysical Chemistry, Groningen, The
Alfred L. Goldberg, Harvard Medical School, Boston, MA
Netherlands
Paul Gollnick, State University of New York at Buffalo, Buffalo, NY
Gerhart Drews, Institut fur Biologie, Freiburg, Germany
Pierre Goldstein, Centre d'lmmunologie INSERM-CNRS de Marseille,
Bernard Dujon, Institut Pasteur, Paris, France
Marseille, France
Edward Egelman, University of Minnesota, Minneapolis, MN
H. Maurice Goodman, University of Massachusetts Medical School,
Jean Marc Egly, Parc d'lnnovation, Illkirch, France Worcester, MA
John Ellis, University of Warwick, Coventry, United Kingdom Horace B. Gray, University of Houston, Houston, TX
Vincent Ellis, Thrombosis Research Institute, London, United Kingdom Neil Green, Vanderbilt University School of Medicine, Nashville, TN
Walther Ellis, Utah State University, Logan, UT WilliamGriffiths, Karolinska Institutet, Stockholm, Sweden
Volker Erdmann, Freie Universitat Berlin, Berlin, Germany Frank Grosse, Institut fur Molekulare Biotechnologie, Jena, Germany
Gerard Evan, ICRF, I:bndon, United Kingdom Marianne Grunberg-Manago, Institut de Biologie Physico-Chemique, Paris,
Kenneth Ewan, Max-Planck Institute of Biophysical Chemistry, Gottingen, France
Germany Peter Gruss, Max-Planck Institute for Biophysical Chemistry, Gottingen,
Hong Fang, Vanderbilt University, Nashville, TN Germany
Lynette R. Ferguson, University of Auckland Medical School, Auckland, Richard Gumport, University of Illinois, Urbana, IL
New Zealand Andras Guttman, Genetich Biosystems, San Diego, CA
Carol A. Fierke, Duke University, Durham, NC William Hagan, College of St. Rose, Albany, NY
J. R. S. Fincham, University of Edinburgh, Edinburgh, Scotland Klaus Hahlbrock, Max-Planck Institut fur Biochemie, Martinsried, Germany
Anthony L. Fink, University of California, Santa Cruz, CA Joshua W. Hamilton, Dartmouth Medical School, Hanover, NH
Gunter Fischer, MPG Arbeitsgruppe, Halle, Germany Susan Hamilton, Baylor College of Medicine, Houston, TX
Darrell R. Fisher, Pacific Northwest Laboratory, Richland, WA Xianlin Han, Washington University School of Medicine, St. Louis, MO
Catherine Florentz, Institut de Biologic Moleculaire et Cellula ire, Ryo Hanai, Rikkyo University, Toshima, Tokyo, Japan
strasbourg, France Yusuf Hannun, Duke University Medical Center, Durham, NC
Ricardo Flores, Instituto de Biologia Molecular y Cellularde Plantas, Stephen E. Harding, University of Nottingham, Sutton Bonington, United
Valencia, Spain Kingdom
P. J. Foley, Thomas Jefferson University, Philadelphia, PA Peter Harland, University of California, Berkeley, CA
Josiane Fontaine-Perus, CNRs, Nantes Cedex, France Ulrich Hartl, Max-Planck Institut fur Biochemie, Martinsried, Germany
R. W. Hartley, National Institutes of Health, Bethesda, MD
Jefferson Foote, Fred Hutchinson Cancer Research Center, seattlf!, WA
Enno Hartmann, Georg-August Universitaet, Gottingen, Germany
Patricia Foster, Boston University, Boston, MA
David L. Haviland, The University of Texas, Houston Health Science
Michel Fougereau, Centre d'lmmunologie Marseille Luminy, Marseille,
Center, Houston, TX
France
Toshihiko Hayashi, University of Tokyo, Tokyo, Japan
Francois Franceschi, Max-Planck Institute for Molecular Genetics, Berlin,
J. K. Heath, University of Birmingham, Birmingham, United Kingdom
Germany
Robert Helling, University of Michigan, Ann Arbor, MI
Murray J. Fraser, Sydney Children's Hospital, Randwick, Australia
Ali Hemmati-Brivanlou, Rockefeller University, New York, NY
Ian Freshney, University of Glasgow, Glasgow, United Kingdom
M. A. Hemminga, Agricultural University of Wageningen, Daagenlaa,
Terrence G. Frey, San Diego State University, San Diego, CA
Laura Frontali, University of Rome, "La sapienza, " Rome, Italy Wageningen, The Netherlands
Beric Henderson, University of Sydney, Westmead, Australia
Yasuo Fukami, Kobe University, Nada, Kobe, Japan
Roger W. Hendrix, University of Pittsburgh, Pittsburgh, PA
Carl W. Fuller, Amersham Pharmacia Biotech, Cleveland, OH
Leonard Herzenberg, Stanford University, Stanford, CA
Betty Gaffney, Florida State University, Tallahassee, FL
George P. Hess, Cornell University, Ithaca, NY
Fernando Garcia-Arenal, Ciudad Universitaria, Madrid, Spain
Christa Heyting, Agricultural University, Wageningen, The Netherlands
Jean-Renaud Garel, Laboratoire de Biologie structurale, CNRs, Gif-sur-
D. J. Hill, St. Joseph's Health Center, London, Ontario, Canada
Yvette, France
James A. Hoch, Scripps Research Institute, La Jolla, CA
D. R. Garrod, University of Manchester, Manchester, United Kingdom
Denis Hochstrasser, Geneva University Hospital, Geneva, Switzerland
Frank R. Gasparro, Jefferson University, Philadelphia, PA
Nicholas A. Hoenich, The University of Newcastle upon Tyne, Newcastle,
C. Gaspin, Centre National de la Researche scientifique, strasbourg, France United Kingdom
Anthony A. Gatenby, E. I. duPont de Nemours & Co., Wilmington, DE Wayne L. Hoffman, University of Texas, Southwestern Medical Center,
Kunihiko Gekko, Hiroshima University, Higashi-Hiroshima, Japan Dallas, TX
CONTRIBUTORS ix
J. John Holbrook, University of Bristol, Bris(ol, United Kingdom Judith E. Layton, Ludwig Institute for Cancer Research, Victoria, Australia
Arne Holmgren, Karolinska Institute, Stockholm, Sweden Claude J. Lazdunski, Laboratoire d'lngeniere des Systemes Macro-
Thomas F. Holzman, Abbot Laboratories, Abbot Park, IL moleculaires, Marseille, France
H. Homareda, Kyorin University, Tokyo, Japan Robin Leake, University of Glasgow, Glasgow, United Kingdom
Roger Hull, John Innes Centre, Colney, Norwich, United Kingdom Stewart H. Lecker, Harvard Medical School, Boston, MA
Martin Hum, University of Texas, Southwestern Medical Center, Dallas, TX Stuart LeGrice, Case Western Reserve School of Medicine, Cleveland, OH
Jennifer A. Hunt, Duke University Medical Center, Durham, NC Ruth Lehmann, New York University, New York, NY
Atsushi Ikai, Tokyo Institute of Technology, Yokohama, Japan Arthur Mo Lesk, University of Cambridge, Cambridge, United Kingdom
Kiyohiro Imai, Osaka University, Osaka, Japan Michael Levine, University of California, Berkeley, Berkeley, CA
Joe Do Lewis, Institute of Cell & Molecular Biology, Edinburgh, United
Taiji Imoto, Kyushu University, Fukuoka, Japan
Antonio Incardona, University of Tennessee, Memphis, TN Kingdom
Uno Lindberg, Stockholm University, Stockholm, Sweden
Edward E. Ishiguro, University of Victoria, Victoria, B.C., Canada
Halina Lis, Weizmann Institute of Science, Rehovot, Israel
Akira Ishihama, National Institute of Genetics, Shizuoka-ken, Japan
Uriel Littauer, Weizmann Institute of Science, Rehovot, Israel
Judith A. Jaehning, University of Colorado, Denver, CO
John Little, University of Arizona, Tucson, AZ
Yuh-Nung Jan, University of California, San Francisco, CA
Lawrence A. Loeb, University of Washington, Seattle, WA
Joel Janin, Laboratoire de Biologie Structurale, Paris, France
Peter Co Loewen, University of Manitoba, Winnipeg, Manitoba, Canada
S. Jansen, Georg-August University Gottingen, Gottingen, Germany
Douglas J. Loftus, National Cancer Institute, National Institutes of Health,
Patricia A. Jennings, University of California, San Diego, La Jolla, CA
Bethesda, MD
Randy L. Jirtle, Duke University, Durham, NC
Kenton Longenecker, University of Virginia Health Sciences Center,
Jonathan Jones, john Innes Institute, Norwich, United Kingdom
Charlottesville, VA
Rick Jones, Southern Methodist University, Dallas, TX
J. Michael Lord, University of Warwick, Conventry, United Kingdom
Hans Jornvall, Karolinska Institutet, Stockholm, Sweden
Martin G. Low, Columbia University, New York, NY
Akia Kaji, University of Pennsylvania, Philadelphia, PA
Reinhard Luhrmann, Institut fur Molekularbiologie und Tumorforschung,
Barton A. Kamen, University of Texas, Southwestern Medical Center,
Marburg, Germany
Dallas, TX
Paul MacDonald, Stanford University, Stanford, CA
Heather Kaminski, Schering-Plough Research Institute, Kenilworth, NJ
Robert M. Macnab, Yale University, New Haven, CT
Minoru Kanehisa, Kyoto University, Kyoto, Japan
Neil B. Madsen, University of Alberta, Edmonton, Alberta, Canada
Jack Kaplan, Oregon Health Sciences University, Portland, OR
Hasaji Maki, Ikoma City, Japan
Francois Karch, University of Geneva, Geneva, Switzerland
Gregory S. Makowski, University of Connecticut, Farmington, CT
Thorn Kaufmann, Indiana University, Bloomington, IN
Jack Maniloff, University of Rochester, Rochester, NY
Jack D. Keene, Duke University, Durham, NC
Jeffrey R. Mann, Beckman Research Institute of the City of Hope, Duarte,
Regis B. Kelly, University of California, San Francisco, CA
CA
Zvi Kelman, Memorial Sloan-Kettering Cancer Center, New York, NY
Bengt Mannervik, Uppsala University, Uppsala, Sweden
Byron Kemper, University of Illinois, Urbana, IL
Armen Manoukian, Ontario Cancer Institute, Toronto, Ontario, Canada
James Kennison, National Institute of Child Health and Human Develop-
Ahmed Mansouri, Max-Planck Institute for Biophysical Chemistry,
ment, National Institutes of Health, Bethesda, Ma
Gottingen, Germany
Kathleen M. Kerr, National Institutes of Health, Bethesda, MD
Mohamed A. Marahiel, Philipps-Universitat Marburg, Marburg, Germany
John R. Kirby, University of California, Berkeley, CA
Guglielmo Marin, Universita Degli Studi di Padova, Padova, Italy
Jennifer Kitchen, Georgetown University, Washington, DC
Susan Marqusee, University of California, Berkeley, CA
Horst Kleinkauf, Technische Universitat, Berlin, Germany Mike Marsh, University College London, London, United Kingdom
Jorg Klug, Phillips-Universitat Marburg, Marburg, Germany Garland Marshall, Washington University, St. Louis, MO
Peter Knight, University of Leeds, Leeds, United Kingdom Jennifer Martin, University of Queensland, Brisbane, Australia
Charlotte Knudsen, University of Aarhus, Aarhus, Denmark Nancy C. Martin, University of Louisville, Louisville, KY
Yuji Kobayashi, Osaka University, Osaka, Japan Florence Maschat, Institut de Genetique Humaine, Montpellier, France
Ralf Koebnik, Biozentrum Basel, Basel, Switzerland Christopher Mathews, Oregon State University, Corvallis, OR
Andrzej Kolinski, Scripps Research Institute, La Jolla, CA Abdul Matin, Stanford University, Stanford, CA
Gerald B. Koudelka, State University of New York at Buffalo, Buffalo, NY Mark Po Mattson, University of Kentucky, Lexington, KY
Joseph Kraut, University of California, San Diego, La Jolla, CA Russell A. Maurer, Case Western Reserve University, Cleveland, OH
Toshio Kuroki, Showa University, Tokyo, Japan Nicola McCarthy, Imperial Cancer Research Fund, London, United
Sidney R. Kushner, University of Georgia, Athens, GA
Kingdom
Kunihiro Kuwajima, University of Tokyo, Tokyo, Japan Richard McCarty, Johns Hopkins University, Baltimore, MD
Harold Lahm, Institute of Molecular Animal Breeding, Munich, Germany David R. McClay, Duke University, Durham, NC
Ratnesh Lal, University of California, Santa Barbara, CA John R. Menninger, University of Iowa, Iowa City, IA
Marc Lalande, Children's Hospital, Boston, MA Carl R. Merril, National Institute of Mental Health, National Institutes of
David Lane, Centre National de la Researche Scientifique, Strasbourg, Health, Bethesda, MD
France David Metzler, Iowa State University, Ames, IA
Janos Lanyi, University of California, Irvine, CA Robert H. Michell, The University of Birmingham, Birmingham, United
Paul Lasko, McGi11 University, Montreal, Quebec, Canada Kingdom
Michael Laskowski Jr ., Purdue University, West Lafayette, IN Marek Mlodzik, European Molecular Biology Laboratory, Heidelberg,
David S. Latchman, University College London Medical School, London, Germany
United Kingdom Evita Mohr, Universitat Hamburg, Hamburg, Germany
Peter Lawrence, Medical Research Council, Cambrid~e, United Kin~dom Ian JoM olineux, University of Texas, Austin, TX
x CONTRIBUTORS
Cesare Montecucco, Universit.1 degli Studi di Padova, Padova, Italy Dietmar Richter, Institut fur Zellbiochemie und klinische Neurobiologie,
Carol Moore, City University of New York Medical School, NY Hamburg, Germany
Henning D. Mootz, Phillips-Universitat Marburg, Marburg, Germany P. G. Righetti, University of Milan, Milan, Italy
Gines Morata, University Autonoma De Madrid, Madrid, Spain Richard J. Riopelle, Queen's University, Kingston, Ontario, Canada
Richard 10M orimoto, Northwestern University, Evanston, IL James Riordan, Harvard University, Boston, MA
John Fo Morrison, The Australian National University, Canberra, Australia Anthony J. Robertson, National Institutes of Health, Research Triangle Park,
Gisela Mosig, Vanderbilt University, Nashville, TN NC
Jan Mous, F. Hoffmann-LaRoche Ltd., Basel, Switzerland Jean-David Rochaix, University of Geneva, Geneva, Switzerland
Mario Roederer, Stanford University, Stanford, CA
Benno Miiller-Hill, Institut fur Genetik / Universitat Koln, Koln, Germany
William A. Rosche, Boston University School of Medicine, Boston, MA
Jo Ko Myers, Texas A&M University, College Station, TX
Kyoshi Nagai, MRC Laboratory of Molecular Biology, Cambridge, United Elliott M. Ross, University of Texas, Southwestern Medical Center, Dallas,
TX
Kingdom
Gregory M. Ross, Queen's University, Kingston, Ontario, Canada
Haruki Nakamura, Biomolecular Engineering Research Institute, Osaka,
Lawrence Rothfield, University of Connecticut, Farmington, CT
Japan
Yoshikazu Nakamura, University of Tokyo, Tokyo, Japan Harry Rubin, University of California, Berkeley, CA
Aiguo Ni, Medical University of South Carolina, Charleston, SC Thomas S. Rush, Princeton University, Princeton, NJ
Allen w. Nicholson, Wayne State University, Detroit, MI M. S. Saedi, Hybritech Co., San Diego, CA
Alan Saltiel, Parke-Davis Pharmaceutical Research, Ann Arbor, MI
Christof Niehrs, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Koich Nishigaki, Saitama University, Urawa, Japan Aziz Sancar, University of North Carolina, Chapel Hill, NC
Ken Nishikawa, National Institute of Genetics, Shizuoka, Japan Matti Saraste, European Molecular Biology Laboratory, Heidelberg,
Ralph Ao Nixon, Harvard Medical School, Belmont, MA Germany
Zuben E. Sauna, National Institutes of Health, Bethesda, MD
Akio Nomoto, University of Tokyo, Tokyo, Japan
Lindsay Sawyer, University of Edinburgh, Edinburgh, United Kingdom
Bengt Norden, Chalmers University of Technology, Gothenburg,
Switzerland Walter Schaffner, Universitat Zurich, Zurich, Switzerland
Shiao Li Oei, Institute I1ir Biochemie, Berlin, Germany Paul Schimmel, Scripps Research Institute, La Jolla, CA
Naotake Ogasawara, Ikoma City, Japan Franz Schmid, Universitat Bayreuth, Bayreuth, Germany
Yoshio Okada, Osaka University, Osaka, Japan Manfred Schnarr, Institut de Biologie Moleculaire et Cellulaire, CNRS,
Charles Ordahl, University of California, San Francisco, CA Strasbourg, France
J. Martin Scholtz, Texas A&M University, College Station, TX
George Ordal, University of Illinois, Urbana, IL
George Oster, University of California, Berkeley, CA Trudi Schupbach, Princeton University, Princeton, NJ
Malcolm G. P. Page, F. Hoffmann-LaRoche Ltd., Basel, Switzerland James Scott, Royal Postgraduate Medical School, London, United Kingdom
Barbara A. Seaton, Boston University, Boston, MA
Renato Paro, University of Heidelberg, Heidelberg, Germany
Do A. Parry, Massey University, Palmerston North, New Zealand Constantin E. Sekeris, University of Wurzburg, Wurzburg, Germany
Premal Ho Patel, University of Washington School of Medicine, Seattle, WA Igor L. Shamovsky, Queen's University, Kingston, Ontario, Canada
Barbara Pearse, MRC Laboratory of Molecular Biology, Cambridge, United Shmuel Shaltiel, Weizmann Institute of Science, Rehovot, Israel
Nathan Sharon, Weizmann Institute of Science, Rehovot, Israel
Kingdom
Israel Pecht, Weizmann Institute of Science, Rehovot, Israel G. Shaw, University of Florida, Gainesville, FL
lain Ko Pemberton, Institut Pasteur, Paris, France William v. Shaw, Leicester University, Leicester, United Kingdom
Bernard Perbal, Centre Universitaire, Orsay, France David Sherman, University of Minnesota, St. Paul, MN
Richard No Perham, University of Cambridge, Cambridge, United Kingdom Ben-Zion Shilo, Weizmann Institute of Science, Rehovot, Israel
Francine Perler, New England Biolabs, Beverly, MA Makoto Shimoyama, Shimane Medical University, Izumo, Japan
Charles L. Perrin, University of California, San Diego, La Jolla, CA Israel Silman, Weizmann Institute of Science, Rehovot, Israel
Steven Perrin, ARIAD Pharmaceuticals, Cambridge, MA Richard J. Simpson, Ludwig Institute for Cancer Research, Victoria,
Bengt Persson, Karolinska Institute, Stockholm, Sweden Australia
Donald Wo Pettigrew, Texas A&M University, College Station, TX Gary Siuzdak, Scripps Research Institute, La Jolla, CA
Larry Pfeffer, University of Te nnessee, Memphis, TN James Skeath, Washington University, St. Louis, MO
Ko Kevin Pfister, University of Virginia, Charlottesville, VA Stephen J. Small, New York University, New York, NY
Margaret A. Phillips, University of Texas, Dallas, TX Colleen M. Smith, Mercer University, Macon, GA
Gerald R. Smith, Fred Hutchinson Cancer Research Center, Seattle, WA
Don Phillips, LaTrobe University, Victoria, Australia
Sarah M. Smolik, Oregon Health Sciences University, Portland, OR
Thomas Lo Poulos, University of California, Irvine, CA
Suzanne G. Sobel, Yale University, New Haven, CT
Linda S. Powers, Utah State University, Logan, UT
Peter EoP revelige, University of Alabama, Birmingham, AL Kunitsugu Soda, Nagaoka University of Technology, Niigata, Japan
Peter Lo Privalov, Johns Hopkins University, Baltimore, MD Lila Solnica-Krezel, Vanderbilt University, Nashville, TN
Mark Solomon, Yale University, New Haven, CT
Gudrun Rappold, Institut fur Humangenetik Universitatsklinikum,
Joseph Sperling, The Hebrew University of Jerusalem, Jerusalem, Israel
Heidelberg, Germany
Stephen Wo Raso, Texas A&M University, College Station, TX Ruth Sperling, The Hebrew University of Jerusalem, Jerusalem, Israel
P0 Do Rathjen, University of Adelaide, Adelaide, Australia Martin Spiess, Biozentrum, Basel, Switzerland
Eo Prekumar Reddy, The Fels Institute for Cancer Research and Molecular Tom Spiro, Princeton University, Princeton, NJ
Biology, Philadelphia, PA Mathias Sprinzl, Universitaet Bayreuth, Bayreuth, Germany
Colin Reese, King's College London, University of London, United Kingdom R. B. Spruijt, Wageningen Agricultural University, Wageningen, The
Peter Reichard, Medical Nobel Institute, Karolinska Institutet, Stockholm, Netherlands
Sweden F. W. Stahl, University of Oregon, Eugene, OR
Steffen Reinbothe, Universite Joseph Fourier, Grenoble, France Martin F. Steiger, F. Hoffmann-LaRoche Ltd., Basel, Switzerland
CONTRIBUTORS xi
Scott Strobel, Yale University, New Haven, CT Graham Warren, Imperial College Research Fund, London, United
Shintaro Sugai, Soka University, Tokyo, Japan Kingdom
Roy Sundick, Wayne State University, Detroit, MI Hans Warrick, Stanford University, Stanford, CA
H. Eldon Sutton, University of Texas, Austin, TX Arieh Warshel, University of Southern California, Los Angeles, CA
Sandra S. Szegedi, University of Illinois at Urbana-Champaign, Urbana, IL Steven A. Wasserman, University of Texas, Southwestern Medical Center,
Sevec Szmelcman, Institut Pasteur, Paris, France Dallas, TX
Hatsumi Taniguchi, University of Occupational and Environmental Health, Hans Weber, Institut fur Molekularbiologie, Zurich, Switzerland
Fukuota, Japan Patricia c. Weber, Schering-Plough Research Institute, Kenilworth, NJ
Joyce Taylor-Papadimitriou, Imperial Cancer Research Fund Laboratories, Eric Westhof, Institut de Biologie Moleculaire et Cellulaire, du CNRS,
London, United Kingdom Strasbourg, France
Mariella Tegoni, CNRS, Marseille, France Richard A. Wetsel, University of Texas, Houston, TX
Jean Thomas, Cambridge University, Cambridge, United Kingdom Paul Whiting, Merck Sharp and Dohme Research Laboratories, Essex,
Carl Thummel, University of Utah, Salt Lake City, UT United Kingdom
Serge Timasheff, Brandeis University, Waltham, MA Peter A. Whittaker, Saint Patrick's College, Maynooth, Kildare, Ireland
Thea D. Tisty, University of California, San Francisco, CA Pernilla Whittung-Stapshede, California Institute of Technology, Pasadena,
Andrew Travers, MRC Laboratory of Molecular Biology, Cambridge, CA
United Kingdom Meir Wilchek, Weizmann Institute of Science, Rehovot, Israel
Jill Trewhella, Los Alamos National Laboratory, Los Alamos, NM
Jim R. Wild, Texas A&M University, College Station, TX
Edward Trifonov, National Institute of Genetics, Shizuoka-ken, Japan
Allison K. Wilson, University of Wisconsin, Madison, WI
Toshiki Tsurimoto, Osaka, Japan
David B. Wilson, Cornell University, Ithaca, NY
Agnes Ullmann, Institut Pasteur, Paris, France
Leslie Wilson, University of California, Santa Barbara, CA
Dominiqe van der Straeten, Universiteit Gent, Gent, Belgium
Sam H. Wilson, NIEHS, National Institutes of Health, Research Triangle
M. van Lijsebettens, Universiteit Gent, Gent, Belgium
Park, NC
Marc Van Montagu, Universiteit Gent, Gent, Belgium
R. Wolfenden, University of North Carolina, Chapel Hill, NC
Klaas van Wijk, Stockholm University, Stockholm, Sweden
Alan Paul Wolffe, NICDH, National Institutes of Health, Bethesda, MD
G. Varani, MRC Laboratory of Molecular Biology, Cambridge, United
C. J. A. M. Wolfs, Wageningen Agricultural University, Wageningen, The
Kingdom
Netherlands
Serge N. Vinogradov, Wayne State University, Detroit, MI
William B. Wood, University of Colorado, Boulder, CO
Hans von Dohren, Technische Universitat Berlin, Berlin, Germany
Robert Woody, Colorado State University, Fort Collins, CO
Edward Voss, University of Illinois, Urbana, IL
Kenneth Yamada, NIDR, National Institutes of Health, Bethesda, MD
Richard Walden, Horticulture Research International, Kent, United
Charles Yanofsky, Stanford University, Stanford, CA
Kingdom
Melinda Wales, Texas A&M University, College Station, TX Ada Yonath, Weizmann Institute of Science, Rehovot, Israel
Valeria A. Wallace, University College London, London, United Kingdom Hiroshi Yoshikawa, Nara Institute of Science & Technology, Ikoma, Japan
Frederick G. Walz, Kent State University, Kent, OH Jennifer Zamanian, University of California, San Francisco, CA
Andrew H. J. Wang, University of lIlinois, Urbana, IL Guiliana Zanetti, University of Milan, Milan, Italy
Hongyun Wang, University of California, Berkeley, CA Amanda Zeffman, MRC Laboratory of Molecular Biology, Cambridge,
James C. Wang, Harvard University, Cambridge, MA United Kingdom
Michael I. Waring, Cambridge University, Cambridge, United Kingdom Suisheng Zhang, Institute of Molecular Biotechnology, Jena, Germany
Amy Warren, Dartmouth College, Hanover, NH Mark Zoller, Ariad Pharmaceuticals, Cambridge, MA
COMMONLY USED ACRONYMS
AND ABBREVIATIONS
A angstrom (10 10 m) G Gibbs free energy of a system
Ab antibody G guanine base
Ac acetyl group G-protein guanine-nucleotide binding regulatory protein
ADP adenosine diphosphate GABA g-aniinobutyric acid
Ala alanine residue (also A) GalNAc JV-acetylgalactosamine residue
AMP adenosine monophosphate GdmCl guanidinium chloride (guanidine hydrochloride)
Arg arginine residue (also R) GDP guanosine diphosphate
Asn asparagine residue (also N) Glc glucose residue
Asp aspartic acid residue (also D) GlcNAc N-acetylglucosamine residue
ATP adenosine triphosphate Gin glutamine residue (also Q)
ATPase adenosine triphosphatase Glu glutamic acid residue (also E)
Gly glycine residue (also G)
Bq becquerel GMP guanoine monophosphate
bp base-pair GSH glutathione, thiol form
BSA bovine serum albumin GSSG glutathione, disulfide form
GTP guanosine triphosphate
C cytosine base
GTPase guanosine triphosphatase
cal calorie (4.18 J)
cAMP 3',5'-cyclie AMP H enthalpy of a system
CD circular dichroism h hour
CoA eoenzyme A His histidine residue (also H)
cDNA complementary DNA HLA histocompatibility locus antigen
cGMP 3',5'-cyclic GMP HPLC high pressure liquid chromatography
Cmc critical micelle concentration Hz hertz, frequency
Cys cysteine residue (also C)
IEF isoeleetric focusing IgG, IgA, IgM, etc.
Da dalton immunoglobuin G, A, M. etc.
DMSO dimethyl sulfoxid^ He isoleucine residue (also I)
DNA deoxyribonucleic acid Ins inositol residue
DNase deoxyribonuclease IR infrared
DTT dithiothreitol
J joule
EDTA ethylenediamine tetraacetic acid
EG [ethylenebis(oxonitrilo)] tetraacetic acid K degrees Kelvin, absolute temperature
EGF epidermal growth factor k rate constant for a specified reaction
ELISA enzyme-linked immunosorbent assay K association constant
a
EM electron microscopy K dissociation constant
d
EPR, ESR electron paramagnetic (or sign) resonance Keq equilibrium constant for a specified reaction
ER endoplasmic reticulum K Michaelis constant
m
EXAFS extended X-ray absorption fine structure kb kilobases
kcal kilocalorie (4.18 kJ)
FAD flavin-adenine dinucleotide kDa kilodalton
fMet JV-formyl methionine
FMN flavin mononucleotide LDL low density lipoprotein
FPLC fast protein liquid chromatography Leu leucine residue (also L)
Lys lysine residue (also K)