Insulin & Related Proteins - Structure to Function and Pharmacology

This book contains contributions presented at the last of the Alcuin Symposia, held in April 2000, as a Festschrift to honour Prof. Axel Wollmer on the occasion of his retirement from the Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen. The Alc

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Insulin & Related Proteins – Structure to Function and Pharmacology Edited by

Markus Leyck Dieken Novo Nordisk Pharma GmbH, Mainz, Germany

Matthias Federwisch Institut für Biochemie, RWTH Aachen, Germany

and

Pierre De Meyts Hagedorn Research Laboratory, Gentofte, Denmark

KLUWER ACADEMIC PUBLISHERS NEW YORK, BOSTON, DORDRECHT, LONDON, MOSCOW

eBook ISBN: Print ISBN:

0-306-47582-0 1-4020-0655-1

©2002 Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow Print ©2002 Kluwer Academic Publishers Dordrecht All rights reserved No part of this eBook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Kluwer Online at: and Kluwer's eBookstore at:

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With compliments from

novo nordisk®

CONTENTS Foreword

ix

Contributors

xi

H. Zahn How Insulin Came From Heidelberg To Aachen and Why It Took five Years.

1

7 D. Brandenburg Insulin at The German Wool Research Institute – Retrospect and Outlook

G.G. Dodson and J.L. Whittingham Insulin: Sequence, Structure and Function - A Story of Surprises

29

41 U. Hassiepen, J. Stahl, B. Motzka and M. Federwisch The Association/Dissociation equilibria of insulin in the presence of metal ions: A Fluorescence Energy Transfer and Circular Dichroism Study

A. Wollmer and T. Mülders Self-association of Insulin Reconsidered I. A Scheme Based on Contact Surfaces

53

T. Mülders and A. Wollmer Self-association of Insulin Reconsidered II. Mathematical Description

67

A. Wollmer T-R Transition

77

P. Krüger Comparison of Conformational Transitions in Proteins

91

M.A. Weiss, Q.-X. Hua, W. Jia, S.H. Nakagawa, Y.-C. Chu, P.G. Katsoyannis 103 Activities of Insulin Analogues at Position A8 are Uncorrelated with Thermodynamic Stability

viii

121 R.H. Jones and F. Shojaee-Moradie Relationships between the Structure of Insulin and its Physiological Effects

P. De Meyts and J. Whittaker Structure-Function Relationships of Insulin and Insulin-Like Growth Factor-I Receptor Binding

131

151 C.W. Ward, T.P.J. Garrett, N.M. MCKern, L.G. Sparrow, M.J. Frenkel Structural Relationships Between Members of the Insulin Receptor Family

C. Kristensen and A.S. Andersen Insulin Interaction with Minimized Receptors and Binding Proteins

165

L. Plum, K. Giesen, R. Kluge, H.-G. Joost Identification of Susceptibility Loci for Obesity, Insulin Resistance, and Hyperglycemia in a Backcross Model of New Zealand Obese (NZO) and Lean SJL MICE

177

189 L. Pellegrini, D.F. Burke and T.L. Blundell Activation Mechanism of fibroblast growth factor receptor tyrosine kinase revealed by crystal structure of fibroblast growth factor receptor ectodomain bound to fibroblast growth factor and heparin.

J. Grötzinger IL-6 type cytokine receptor complexes

201

F. Bost, Y.-M. Yang, C. Liu, W. Charbono, N. Dean, R. McKay, X.-P. Lu, 213 O. Potapova, M. Pfahl and D. Mercola Inhibition of growth factor stimulated