Table Of ContentDNA-Ligand
Interactions
From Drugs
to Proteins
NATO ASI Series
Advanced Science Institutes Series
A series presenting the results of activities sponsored by the NA TO Science Committee,
which aims at the dissemination of advanced scientific and technological knowledge,
with a view to strengthening Jinks between scientific communities.
The series is published by an international board of publishers in conjunction with the
NATO Scientific Affairs Division
A Life Sciences Plenum Publishing Corporation
B Physics New York and London
C Mathem"tical D. Reidel Publishing Company
and Physical Sciences Dordrecht, Boston, and Lancaster
D Behavioral and Social Sciences Martinus Nijhoff Publishers
E Engineering and The Hague, Boston, Dordrecht, and Lancaster
Materials Sciences
F Computer and Systems Sciences Springer-Verlag
G Ecological Sciences Berlin, Heidelberg, New York, London,
H Cell Biology Paris, and Tokyo
Recent Volumes in this Series
Volume 131-Fat Production and Consumption:
Technologies and Nutritional
Implications
edited by C. Galli and E. Fedeli
Volume 132-Biomechanics of Cell Division
edited by Nuri Akkas
Volume 133-Membrane Receptors, Dynamics, and Energetics
edited by K. W. A. Wirtz
Volume 134-Plant Vacuoles: Their Importance in Solute Compartmentation in
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edited by B. Marin
Volume 135-Signal Transduction and Protein Phosphorylation
edited by L. M. G. Heilmeyer
Volume 136-The Molecular Basis of Viral Replication
edited by R. Perez Bercoff
Volume 137-DNA-Ligand Interactions: From Drugs to Proteins
edited by Wilhelm Guschlbauer and Wolfram Saenger
Series A: Life Sciences
DNA-Ligand
Interactions
From Drugs
to Proteins
Edited by
Wilhelm Guschlbauer
Centre d'Etudes Nucleaires de Sac lay
Gif-sur-Yvette, France
and
Wolfram Saenger
Freie Universitat Berlin
Berlin, Federal Republic of Germany
Plenum Press
New York and London
Published in cooperation with NATO Scientific Affairs Division
Proceedings of a NATO ASI/FEBS Course on
DNA-Ligand Interactions: From Drugs to Proteins,
held August 30-September 11,1986,
in Abbey of Fontevraud, France
Library of Congress Cataloging in Publication Data
NATO ASI/FEBS Course on DNA-Ligand Interactions: From Drugs to Proteins
(1986: Abbey of Fontevraud)
DNA-Ligand Interactions.
(NATO ASI series. Series A, Life sciences; v. 137)
"Proceedings of NATO ASI/FEBS Course on DNA-Ligand Interactions: From
Drugs to Proteins, held August 30-September 11, 1986, in Abbey of Fontevraud,
France"-T.p. verso.
"Published In cooperation with NATO Scientific Affairs Division."
Includes bibliographies and Index.
1. Deoxyribonucleic aCid-Congresses. 2. Protein binding-Congresses. 3.
Drugs-Metabolism-Congresses. I. Guschlbauer, Wilhelm. II. Saenger,
Wolfram. III. NATO Advanced Study Institute. IV. Federation of European
Biochemical Societies. V. North Atlantic Treaty Organization. Scientific Affairs
Division. IV. Title. VII. Series. [DNLM: I. Molecular Biology-congresses. 2. Poly
nucleotide Synthetases-metabolism-congresses. QU 58 N27935d 19861
QP624.N38 1986 574.87'3282 87-20339
ISBN 978-1-4684-5385-0 ISBN 978-1-4684-5383-6 (eBook)
00110.1007/978-1-4684-5383-6
© 1987 Plenum Press, New York
Softcover reprint of the hardcover 1s t edition 1987
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
All rights reserved. No part of this book may be reproduced, stored in a retrieval system,
or transmitted in any form or by any means, electronic, mechanical, photocopying,
microfilming, recording, or otherwise, without written permission from the Publisher
NATO Advanced Study Institute 20/86
FEBS Advanced Course 08/86
Organizing Committee
Wilhe 1m GUSCHLBAUB: R, Director
Service de Biochimie, Bat. 142, Departement de Biologie
Centre d'B:tudes Nucleaires de Saclay
F -91191 Gif-sur-Yvette Cede>:, France
Wolfram SAB:NGB:R, Codirector
Institut fur Kristallographie, Freie Universitat
Takustrasse 6
D-1000 Berlin 33, German Federal Republic
Michael WARING Marc LB:NG
Department of Pharmacology Centre de Biophysique l-lolecwlaire du CNRS
University of Cambridge, Hills Road lA, Ave. de la Recherche Scientifique
Cambridge CB2 ZQQ, U.K. 45045 Orlhns Cede:<, France
ACKNOWLB:DGB:MB:NTS
This Advanced Study Institute was held in the Centre Culturel de l'Ouest (Royal Abbey of
Fontevraudl near Saumur (Francel from August 30th to September 11 th, 1986 under the
auspices of the North Atlantic Treaty Organization (NATO) and the Federation of European
Biochemical Societies (FEBS).
The following institutions and companies have sponsored the participation of students at this
ASI:
National Science Foundation, Washington, D.C., U.S.A.
ORIS-Industrie, Paris, France
Departement de Biologie, Centre d'e:tudes Nucleaires de Saclay, Gif-sur-Yvette, France
Schering A.G., Berlin, G.F .R.
Fa rmitalia - Carlo e:rba, S.p.A., Milano, Italy
Hoffmann-Laroche &. Co. Ltd., Basle, Switzerland
Institut Scientifique Roussel - Roussel-Uc1af, Paris, France
Institut de Recherches Internationaies Servier, Neuilly-sur-Seine, France
Inf-Biorecherches, Castanet Tolosan, France
ligue Fran~aise contre Ie Cancer, Paris, France
L'Oreal, Clichy, France
Support received from the following companies and institutions is also acKnowledged:
Boehringer-Mannheim France, Meylan, France
BruKer - Spectrospin, Wissembourg, France
Jobin-Yvon ISA, Longjumeau, France
PerKin glmer France, Bois d'Arcy, France
Siemens A.G., Darmstadt, G.F .R.
Region des Pays de la Loire, Nantes, France
Centre Culture 1 de l'Ouest, Fontevraud, France
Free advertising was offered by the following Journals:
NUCLll:IC ACIDS RESEARCH and EMEO JOURNAL URL Press Ltd., Eynsham, Oxford, U.K.)
JOURNAL OF EIOMOLECULAR STRUCTURE AND DYNAMICS (Adenine Press, Guilderland
NY, USA)
BIOCHIMIE (Soci~te de Chimie Biologique, Paris, France)
vi
PREFACE
This volume contains the texts of the nineteen lectures presented at the NATO-ASI -
FEBS Course on "DNA - ligand interactions: from drugs to proteins." The Advanced Study
Institute (ASIl was held from August 30th to September 11th. 1986 in the Abbey of
Fontevraud (France). The ASI was attended by 112 participants from a wide scientific horizon
and from twentyone different countries. It was in some way a follow-up of the ASI held in
Maratea. Italy in May 1981 and which was published in the NATO ASI Life Science series as
volume 45.
While much has been learned about the way the cellular machinery maintains and transmits
the genetic heritage. as well as how these processes are regulated. little is Known about how
the interactions between the various partners involved are taKing place. The interactions of
drugs and proteins with nucleic acids are of evident importance in the understanding of these
problems.
The spectacular advances in recombinant DNA technology and the increased sophistication
of biophysical techniques. in particular >:-ray diffraction and nuclear magnetic resonance.
have created a scientific environment which is highly promising for the future of research in
molecular biology. These advances permH the serious hope that biology on the molecular level
may become a r-eality. Some of the contributions at the ASI presented the most recent
advances in this e>:citing field.
To understand fully the posssibilities of these techniques. structural biologists have to
learn about the problems of modern biology and molecular biologists have to become familiar
with the new structural techniques. We realized that only such an interrlisclplinary approach
can be crowned by success and this ASI was planned and organized around this idea.
The choice of the subjects and lecturers was directed by the desire to present few. but
particularly interesting biological problems in a concise way and then to offer various
aspects of the way how physico-chemical and biochemical methodology can attacK them. For
reasons of time limitation only few subjects could be selected. Therefore several highly
interesting. but voluminous subjects were excluded from the programme. liKe chromatin
structure or RNA - protein interactions. We preferred to concentrate on a few preCise
problems which are actively- advancing. The scientific content of the interdisciplinary Study
Institute centered around the following subjects:
*
DNA structure. its role in gene regulation. DNA hydration and interaction with drugs.
*
Repressors: interactions with operators. structure and function.
*
Methylases and restriction nucleases: role in regulatory processes. structure and mode
of action.
*
Finally. an outlooK at a much more complicated system: DNA - antibody interactions.
From the various contributions in this volume it can be seen that even this volontarily
limited content demands interest in such varied subjects as genetics. enzymology.
spectroscopy. physical chemistry. pharmacology and crystallography.
In addition to the 19 lectures. three round table discussions on the three main themes
were held. The active involvement of the participants was manifested by 18 research seminars
and 48 posters. presented in three poster sessions.
vii
The choice of Fontevraud Abbey was also
a deliberate one: a quiet place at the
crossroad of cultural influences. one of the
spiritual centers of Western Europe for six
centuries. it contains such significant relics
as the tombs (with their colored reclining
effigies) of Richard lionheart and his
parents. Henry II. King of England and
Ali~nor d'Aquitaine. This grandiose Abbey.
rich in history and architecture in one of the
most beautiful regions of Europe has now
been converted. after 150 years as a prison,
into a Seminar Center, the Centre Culturel de
l'Ouest. Within the first days several
participants noticed a gothic angel <left> on
one of the vaults of the refectory holding an
ominous attribute: a braided ring, a
left-handed helical cirde. Some unKnown
stone mason five hundred years ago must
have forseen that some day plasmids will be
discovered.
In conclusion the organizers wish to thanK their colleagues, Michael Waring and Marc Leng,
for their help in the early stages of the organization of the ASI. We are also grateful to all
participants for contributing to stimulating discussions and to the excellent atmosphere. We
thanK, in particular. the lecturers for their brilliant contributions and for producing their
manuscripts in due time. The lecturers also Kindly furnished the reading material which was
made available to the participants in four ring binders in the entrance of the lecture hall. Our
thanKs go to the staff of the Centre Culture I de l'Ouest in the Abbey of Fontevraud for their
constant attention and, in particular. to Miss Annie Guillet, responsible of the Meeting
Department of the Centre. Last. but not least, our thanKs go to my faithful collaborator. Miss
Anne Woisard, who tirelessly was troubleshooting. taxiing people around, maKing phone calls,
accompanying buses and helping whenever necessary. before, during and after the meeting.
Merci, Anne.
The editors hope that this volume will find its way on the desKs and into the laboratories
of researchers and students aliKe as an interdisciplinary text and important source of
reference material.
View of the Abbey of Fontevraud from the South.
Wilhelm Guschlbauer
Wolfram Saenger
December 1986
viii
CONTENTS
Al DNA Structure and Interaction with Small Molecules
DNA structure: Current results from single crystal x-ray diffraction studies
O. Kennard
One-and two- dimensional NMR studies of the structures of simple sequence DNAs 23
D.R. Kearns
The major and minor grooves of the DNA helix as conduits for information transfer 45
R.I!:. Dickerson*, M.L. Kopka and P.I!:. Pjura
Unusual DNA structures and gene regulation 63
R.D. Wells
Specificity and dynamics of protein - nucleic acid interactions .••••••••••••••••• 85
D. Porschke
DNA and its counterions: metal ions, amino acids, histones and protamines 105
J. Subirana
Dynamic aspects of antibiotic - DNA interaction 113
M. Waring
Specific gene regulation of oligodeoxynucleotides covalently
linked to intercalating agents •••••••••••••••.•••••••••••••.•••••• 127
C. Hfltne
Pharmacology of DNA binding drugs 141
E. Lambert and J.-B. LePecq
Bl DNA - Protein Interactions: Repressor - Operator Systems
On the nature and specificity of DNA-:"protein interactions
in the regulation of gene expression ....................................... 159
P.H. von Hippel and O.G. Berg
Searching for the code of ideal protein-DNA recognition ........................ 173
N. Lehming, J. Sartorius. E. von Wilcken-Eergmann and B. Mueller-Hill
:!!:Q Repressor. a crystallographic study of allostery in genetic regulation. • • • • • • • • .. 183
P.E. Sigler. A. Joachimiak. R.W. Schevitz. C.L. Lawson. R.-G. Zhang. Z. Otwinowski
and R. Marmorstein
ix
structural studies of three DNA binding proteins: catabolite gene activator protein.
resolvase and the Klenow fragment of DNA polymerase I ••••••••••••••• 185
T.A. Steitz. L. Beese, B. Engelman, P. Fremont, J. Friedman, M. Sanderson,
S. Schultz, G. Shields and J. Warwitker
A two-dimensional NMR study of the complex of lac repressor headpiece
with a 14 bASe pair lac operatDl' fragment. • • • • • • • • • • • • • • • • • • • • • • • • 191
R. Boelens, R.M. Scheek, R.M.J.N.lamerichs. J. de Vlieg. J.H. van Boom
and R. Kaptein
a
DNA - Protein Interactions: Methylation and Restriction Enzymes.
DNA methylation and mismatch repair: molecular specificities. • • • • • • • • • • • • • • • • 217
M. Radman
Recognition of DNA sequences by restriction endonudeases • • • • • • • • • • • • • • • • • • 225
G. Maass
Mechanism and specificity of two restriction enzymes, Caul and CaulI.
that recognize asymmetrical DNA sequences ••••••••••••••••••••••• 239
S.P. Bennett and S.g. Halford
Structure of the DNA-gcoRI endonucleASe recognition complex ••••••••••••••••• 251
J.M. Rosenberg. J.A. McClarin. C.A. Frederick. B.-C. Wang. J. Grable.
H.W. Boyer and P. Greene
Dl Outlook: DNA-Protein Interactions of Complex Systems
Antibodies to nucleic acids 257
M. Leng
Summary and Conclusions 269
W. Saengttr
Research Seminars •••••••••••••••••••••••••••••••••••••••••••••••••. 275
Posters •••••••••••••••••••••••••••..• ,........................... 277
Participants .............. 281
I ••••••••••••••••• " I •••••••••••••••• I • • •
Index .•....•••••.••.•..•..•..••...••.•....•...•..•.•••.•..••...•. 285
*
In multi-author articles the speaker's name is in bold face print.
x
