Table Of Content

EXS 73 Interface between Chemistry and Biochemistry Edited by P. Jolles H. J6rnvall Birkhauser Verlag Basel . Boston . Berlin Editors Prof. Dr. P. Jolles Prof. Dr. H. Jiirnvall Laboratoire des Proteines Department of Medical Biochemistry and Universite Rene Descartes Biophysics 45, rue des Saints-Peres Karolinska Institutet F-75270 Paris Cedex 06 S-17177 Stockholm France Sweden Library of Congress Cataloging-in-Publication Data Interface between chemistry and biochemistry I edited by P. Jolles, H. Jiirnvall. (EXS; 73) Includes bibliographical references and index. ISBN -13 :978-3-0348-9889-8 I. Biochemistry. 2. Analytical biochemistry. I. Jolles, Pierre, 1927- . II. Jiirnvall, Hans. III. Series. QP514.2.I57 1995 574.19'2--dc20 Deutsche Bibliothek Cataloging-in-Publication Data EXS. - Basel; Boston; Berlin: Birkhiiuser. Fraher Schriftenreihe Fortlaufende Beil. zu: Experientia 73. Interface between chemistry and biochemistry. - 1995 Interface between chemistry and biochemistry I ed. by P. Jolles ; H. Jiirnvall.-Basel; Boston; Berlin: Birkhiiuser, 1995 (EXS; 73) ISBN -13 :978-3-0348-9889-8 e-ISBN-13 :978-3-0348-9061-8 DOl: 10.1007/978-3-0348-9061-8 NE: Jolles, Pierre [Hrsg.J The publisher and editor can give no guarantee for the information on drug dosage and administration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. For any kind of use permission of the copyright owner must be obtained. © 1995 Birkhiiuser Verlag, PO Box 133, CH-401O Basel, Switzerland Softcover reprint of the hardcover 1st edition 1995 Printed on acid-free paper produced from chlorine-free pulp. 00 ISBN -13 :978-3-0348-9889-8 987654321 Contents Foreword P. Jolles and H. Jornvall. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. VII Chemistry at interfaces and in transport F. Carriere, R. Verger, A. Lookene and G. Olivecrona Lipase structures at the interface between chemistry and biochem~ istry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 G. Vandenbussche, J. Johansson, A. Clercx, T. Curstedt and J.-M. Ruysschaert Structure and orientation of hydrophobic surfactant-associated proteins in a lipid environment . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 M.N. Gupta Enzyme function in organic solvents. . . . . . . . . . . . . . . . . . . . . . . . . 49 G. von Heijne Protein sorting signals: Simple peptides with complex func- tions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 Chemistry and biochemistry J. Jeffery Enzymes: Chemistry and biochemistry . . . . . . . . . . . . . . . . . . . . . . . 79 E. Appella, E.A. Pad/an and D.£. Hunt Analysis of the structure of naturally processed peptides bound by Class I and Class II major histocompatibility complex molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 105 R.A. Lerner and K.D. Janda Catalytic antibodies: Evolution of protein function in real time. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 121 Analysis of proteins and nucleic acids A.S. Inglis, G.E. Reid and R.J. Simpson Chemical techniques employed for the primary structural analysis of proteins and peptides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 141 T. Douki and J. Cadet UV and nucleic acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 Synthesis of active compounds M. Schl/ltz and H. Kunz Chemical and enzymatic synthesis of glycopeptides . . . . . . . . . . .. 201 A. Unden and T. Bartfai Peptides as active probes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 229 Metalloproteins B.L. Vallee and D.S. Auld Zinc metallochemistry in biochemistry . . . . . . . . . . . . . . . . . . . . . .. 259 R.M.A. Knegtel, M.A.A. van Tilborg, R. Boelens and R. Kaptein NMR Structural studies on the zinc finger domains of nuclear hormone receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 279 Subject index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 297 Foreword The developing importance of the interface between chemistry and biology is probably the largest change to have occurred in chemistry in the past 15 years. Increasingly more chemists work on problems dealing with biology, and interfacial research is poised to move into the main stream of both disciplines. This merging of two types of approach has resulted in a vigorous research discipline with unprecedented potential to address important biological and chemical problems. A series of exam ples is developed in this book. Analytical aspects are discussed in several chapters. Fundamental concepts do not only derive from chemistry, but chemistry has provided biochemistry with powerful tools of analysis. Equally important, phys icochemical methods allow studies of nucleic acids and lipids, lipases, receptors and other membrane proteins. Several chapters deal with enzymes in different contexts. The part devoted to metalloproteins is directed toward zinc metallochemistry and NMR structural work on zinc proteins. Chemists have been able to bring to biology their characteristic approach of synthesizing new molecules. These aspects are treated in chapters devoted to glycopeptides and uses of peptides as probes. Further fields of interest in combining different disciplines concern novel active compounds, such as surfactant peptides and catalytic antibodies in studies resulting from close collaboration between chemists and bio chemists. Combined, all chapters illustrate the broad approaches used in modern research and the frequent use of both methods and subjects at the interface between different fields, be it chemistry and biochemistry, antibodies and enzymes, metals and proteins, transport and static molecules, or hydrophobicity and hydrophilicity. Pierre Jolles and Hans Jornvall Universite de Paris V and Karolinska Institutet Paris and Stockholm, January 1995 Chemistry at interfaces and in transport Intertace between Chemistry and Biochemistry ed. by P. Jollas and H. Jomvall © , 995 Birkhauser Verlag Basel/Switzerland Lipase structures at the interface between chemistry and biochemistry F. Carrierel, R. Vergerl, A. Lookene2 and G. Olivecrona2 'Laboratoire de Lipolyse Enzymatique, CNRS, B.P. 71, F-13402 Marseille cedex 9, France 2Department of Medical Biochemistry and Biophysics, Umea University, S-90187 Umea, Sweden Summary. In this chapter we review recent molecular knowledge on two structurally related mammalian triglyceride lipases which have evolved from a common ancestral gene. The common property of the lipase family members is that they interact with non-polar sub stances. Pancreatic lipase hydrolyzes triglycerides in the small intestine in the presence of many dietary components, other digestive enzymes and high concentrations of detergents (bile salts). Lipoprotein lipase acts at the vascular side of the blood vessels where it hydrolyses triglycerides and some phospholipids of the circulating plasma lipoproteins. A third member of the gene family, hepatic lipase, is found in the liver of mammals. Also, this lipase is involved in lipoprotein metabolism. The three lipases are distantly related to some non-cata lytic yolk proteins from Drosophila (Persson et aI., 1989; Kirchgessner et aI., 1989; Hide et aI., 1992) and to a phospholipase AI from hornet venom (Soldatova et aI., 1993). Introduction Exocrine lipases are soluble enzymes that bind to lipid/water interfaces where they catalyze hydrolysis of the water-insoluble lipids to more polar products which can then be incorporated into cell membranes and be used in further metabolic processes. Lipases differ from other es terases in that their substrates are insoluble and therefore aggregated. It follows that lipases carry out catalysis in a heterogeneous system. Their activity is usually maximal only when the enzyme is adsorbed to a lipid/water interface. This catalytic property, known as "interfacial activation", was first described by Sarda and Desnuelle, who proposed a conformational change of the enzyme at the interface (Sarda and Desnuelle, 1958). The theoretical treatment of lipase kinetics at the interface was previously reviewed (Verger and deHaas, 1976). In recent years a structural basis for the action of lipases was revealed through high-resolution X-ray crystallography of some microbiallipases (Rhizomucor miehei (Brady et al., 1990; Brzozowski et al., 1991), Geotrichum candidum (Schrag et al., 1991), Candida rugosa (Grochulski et al., 1993), Pseudomonas glumae (Noble et al., 1993), and Candida antartica (Uppenberg et al., 1994), of cutinase (Martinez et al., 1992), as well as of a mammalian triglyceride lipase (human pancreatic lipase (Winkler et al., 1990». The active sites contain a charge-relay triad of Ser, His and Asp/Glu, similar to what was known from serine proteases. An additional feature of the lipases is that their active sites are hidden 4 F. Carriere et at. 1600 A 1400 ~OIl 1200 § 1000 '-' ..>... . :E ..... 800 Saturation 1e;u,1 a1.;=,1 600 '0 ~ Q.. rJJ 400 200 2 3 4 Tributyrin (mM) 14000 B 12000 ~OIl 10000 § '-' ....>..... . 8000 .: = ..... 1e;u,1 6000 1;,1 a.= o HPL -colipase '0 ~ 4000 • HPL + colipase Q.. rJJ 2000 0 0 2 3 4 Sodium taurodeoxychoJate (mM)