Table Of Content

Ma.ss Spectrometry in Biology & Medicine Ma.ss Spectrometry in Biology & Medicine Edited by A. L. Burlingame University of California, San Francisco, CA Steven A. Carr SmithKline Beecham Pharmaceuticals, King ofP russia, PA Michael A. Baldwin University of California, San Francisco, CA Springer Science+Business Media, LLC © 2000 Springer Science+Business Media New York OriginaIly published by Humana Press Inc. Softcover reprint of the hardcover 1s t edition 2000 For additional copies, pricing for bulk purchases, and/or information about other Humana titles, contact Humana at the above address or al any of the following numbers: Tel: 973-256-1699; Fax: 973-256-8341; E-mail: MASS SPECTROMETRY IN BIOLOGY AND MEDICINE Dedicated to the memory of our dear colleague and friend Wilhelm J. Richter v MASS SPECTROMETRY IN BIOLOGY AND MEDICINE Table of Contents Organizing Committee/Sponsors ....................................................................... xi Preface.. ......... .................. ...... .. .. .............. .. .. .. ... ... ..... ..... .. . ... .. ... ..... .... ... ... . ..... ... xiii A New Delayed Extraction MALDI-TOF MS-MS for Characterization of Protein Digests Marvin Vestal, Peter Juhasz, Wade Hines, and Stephen Martin ...................... 1 Measurements of Protein Structure and Noncovalent Interactions by Time-of-Flight Mass Spectrometry With Orthogonal Ion Injection A. N. Krutchinsky, I. V. Chernushevich, A. V. Loboda, W. Ens and K. G. Standing ............................................................................................ 17 Isotopic Amplification, HID Exchange, and Other Mass Spectrometric Strategies for Characterization of Biomacromolecular Topology and Binding Sites Alan G. Marshall, Mark R. Emmett, Michael A. Freitas, Christopher L. Hendrickson and Zhongqi Zhang ............................................ 31 Probing the Nature of Amyloidogenic Proteins by Mass Spectrometry Ewan J. Nettleton and Carol V. Robinson ....................................................... 53 Studying Noncovalent Small Molecule Interactions with Protein and RNA Targets by Mass Spectrometry Joseph A. Loo, Venkataraman Thanabal and Houng-Yau Mei ...................... 73 Identification of Protein-Protein Interfaces by Amide Proton Exchange Coupled to MALDI-TOF Mass Spectrometry Jeffrey G. Mandell, Arnold M. Falick and Elizabeth A. Komives ................... 91 Electron Capture Dissociation Produces Many More Protein Backbone Cleavages Than Collisional and IR Excitation Roman A. Zubarev, Einar K. Fridriksson, David M. Horn, Neil L. Kelleher, Nathan A. Kruger, Mark A. Lewis, Barry K. Carpenter and Fred W. McLafferty .................................................................................. 111 Protein Micro-Characterization by Mass Spectrometry: Sample Handling and Data Flow Paul Tempst, Hediye Erdjument-Bromage, Matthew C. Posewitz, Scott Geromanos, Gordon Freckleton, Anita Grewal, Lynne Lacomis, Mary Lui and John Philip .............................................................................. 121 vu TABLE OF CONTENTS Towards an Integrated Analytical Technology for the Generation of Multidimensional Protein Expression Maps Paul A. Haynes, David R. Goodlett, Steven P. Gygi, Julian D. Watts, Daniel Figeys and Reudi Aebersold ................................................................ 143 Sequencing the Primordial Soup Jeffrey Shabanowitz, Robert E. Settlage, Jarrod A. Marto, Robert E. Christian, Forest M. White, Paul S. Russo, Susan E. Martin and Donald F. Hunt .......... 163 Coaxial Nanospray Coupled with a Hybrid Quadrupolel Time-of-Flight Tandem Mass Spectrometer for Proteome Studies M. A. Moseley ................................................................................................... 179 Life Without Databases: De Novo Sequencing of Small Gene Products and Complete Characterization of Posttranslational Modifications Roland S. Annan, Michael J. Huddleston, Dean E. McNulty and Steven A. Carr .......................................................................................... 199 Investigation of Intact Subunit Polypeptide Composition of the 20S Proteasome Complex from Rat Liver Using Mass Spectrometry Lan Huang, C. C. Wang and A. L. Burlingame ............................................. 217 Deciphering Functionally Important MuItiprotein Complexes by Mass Spectrometry Andrej Shevchenko and Matthias Mann ........................................................ 237 Investigation of Apoptosis-Involved Processes by Mass Spectrometric Identification of the Apoptosis-Associated Proteins in IgM-Induced Burkitt Lymphoma Cells Eva-Christina Maller, Brigitte Wittmann-Liebold and Albrecht Otto .......... 271 IR-MALDI - Softer Ionization in MALDI-MS for Studies of Labile Macromolecules R. Cramer and A. L. Burlingame .................................................................... 289 Identification of in-vivo Phosphorylation Sites with Mass Spectrometry Xiaolong Zhang, Christopher J. Herring and Jun Qin ................................. 309 Determination of Enzyme Mechanisms by Stopped-Flow Electrospray Mass Spectrometry Frank B. Simpson and Dexter B. Northrop .................................................... 329 Glycosylation of Proteins - A Major Challenge in Mass Spectrometry and Proteomics Gerald W. Hart, Robert N. Cole, Lisa K. Kreppel, C. Shane Arnold, Frank 1. Comer, Sai Iyer, Xiaogang Cheng, Jill Carroll and Glendon J. Parker ........3 65 viii MASS SPECTROMETRY IN BIOLOGY AND MEDICINE Site-specific Characterization of the N-linked Glycans of Murine PrpSc Using Advanced Methods of Electrospray Mass Spectrometry Elaine Stimson, James Hope, Angela Chong and Alma L. Burlingame .. ..... 383 Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of N-Linked Carbohydrates and Related Compounds David J. Harvey, Bernhard Kuster, Susan F. Wheeler, Ann P. Hunter, Robert H. Bateman and Raymond A. Dwek .................................................. 403 Electrophoretic and Mass Spectrometric Strategies for the Identification of Lipopolysaccharides and Immunodeterminants in Pathogenic Strains of Haemophilus influenzae; Application to Clinical Isolates P. Thibault, J. Li, A. Martin, J. C. Richards, D. W. Hood and E. R. Moxon .............................................................................................. 439 Mycobacterial Lipoglycans: Structure and Roles in Mycobacterial Immunity J. Nigou, B. Monsarrat, M. Gilleron, T. Brando, R. Albigot and G. Puzo ...................................................................................................... 463 The Impact of Drug Metabolism in Contemporary Drug Discovery: New Opportunities and Challenges for Mass Spectrometry Thomas A. Baillie and Paul G. Pearson ......................................................... 481 Electrospray Mass Spectrometric Analysis of Lipid Mediators Derived from Arachidonic Containing Membrane Phospholipids Robert C. Murphy and Tatsuji Nakamura ..................................................... 497 Mass Spectrometry After the Human Genome Project Charles R. Cantor ............................................................................................ 515 Problems and Prospects in the Characterization of Posttranscriptional Modifications in Large RNAs Pamela F. Crain, Duane E. Ruffner, Yeunghaw Ho, Fenghe Qiu, Jet Rozenski and James A. McCloskey ................................................................................. 531 Appendix .......................................................................................................... 553 Author Index .................................................................................................... 563 Subject Index ................................................................................................... 565 ix MASS SPECTROMETRY IN BIOLOGY AND MEDICINE Organizing Committee Co-Chairs A. L. Burlingame, University of California, San Francisco, CA Steven A. Carr, SmithKline Beecham Pharmaceuticals, PA Wilhelm J. Richter, Ludwig Institute for Cancer Research, UK Conference Coordinator Marilyn F. Schwartz, University of California, San Francisco, CA Members Robert Anderegg, Glaxo Wellcome Inc., NC Robin T. Aplin, Oxford University, UK Thomas A. Baillie, Merck, PA Catherine E. Costello, Boston University, MA Bhupesh C. Das, CNRS, France Simon J. Gaskell, UMIST, UK Emilio Gelpi, IIBB-CSIC, Spain Michael L. Gross, Washington University, MO Karl-Anders Karlsson, Gothenburg University, Sweden Gennaro Marino, University of Naples, Italy Takekiyo Matsuo, Osaka University, Japan James A. McCloskey, University of Utah, UT Robert A. Murphy, National Jewish Hospital, CO Scott D. Patterson, Amgen Inc., CA Jasna Peter-Katalinic, Universitat Munster, Germany Peter Roepstorff, Odense University, Denmark Jan Sjovall, Karolinska Institutet, Sweden Sponsors Affymax Research Institute N euroSearch AlS Amgen Nippon Kayaku Co., Ltd. Astra Hassle AB Novartis Pharmaceuticals Corporation Baxter Healthcare Corporation Otsuka Pharmaceuticals Co., Ltd. Bristol-Myers Squibb Co. Parke-Davis Pharmaceutical Research Finnigan Corporation PE Biosystems Genecor International, Inc. Pfizer, Inc. Genentech, Inc. Phyto Lierac Glaxo Wellcome Inc. Proctor & Gamble Pharmaceuticals Institut Henri Beaufour Sankyo Co., Ltd. Isotec Inc. SmithKline Beecham Pharmaceuticals Kratos Analytical Instruments Sumitomo Chemical Co., Ltd. Merck & Co., Inc. Zeneca Ag Products Micromass, Inc. Zeneca Pharmaceuticals We regret the passing of our esteemed colleague, Prof. Takekiyo Matsuo, in 1998. Xl MASS SPECTROMETRY IN BIOLOGY AND MEDICINE Preface As mass spectrometry enters its second century following the discoveries of the electron and ions by J. J. Thomson, no one could have anticipated the developments of the last decade that initiated structural studies of biomacro- molecules, and even the detection and measurement of their mega-dalton noncovalent complexes and assemblages. This was not brought about by painstak- ing refinements of existing methods, but resulted from the discovery of new processes of ion formation from polar substances in liquid or solid solution that avoid chemical derivatization and/or destructive sample vaporization. New types of mass spectrometers are needed to exploit the inherent sensitivities of these high efficiency ion sources and permit routine realization of high mass resolution and accuracy of mass measurement. Ofe qual importance for sequencing and detailed structural characterization of components ofbiopolymers is the need to develop tandem instrumentation with optimized sensitivity able to produce high quality product ion spectra. Considerable attention is currently focused on sample isolation and handling methodologies. Resolution of these issues is critical for successful work in the femto- and attomole ranges. Biological problems involving protein macromolecules, for example, usually require dealing with complex mixtures, such as immunoprecipitates, celllysates, or molecular machines, that are in many cases well suited to SDS PAGE methods. These technologies mesh well with mass spectrometry and genomics. Hence, the digestion, extraction, and identification of peptides from gel spots using these mass spectrometric mapping and de novo peptide sequencing methods can be combined successfully with rapid protein identification by interrogation of protein, gene, and EST databases. However, concerns over how to analyze components of low abundance in the presence of many others with differing properties in widely varying amounts is an unsolved problem. IN the context of cell biology, the detection and identification oflow copy number gene expression in a cell milieu is a daunting task. In addition, effective separation of membrane proteins remains a challenge, although amenable to electrospray measurement using suitable solvents. The detection and identification of DNA polymorphisms is readily tractable using chip-based robotics and mass spectrometric readout technologies. To gain an understanding of the functional details of the machinery of cells, it is necessary to define the physiologically active forms of proteins and their modes of regulation. This requires a knowledge oftheir myriad posttranslational and xenobiotic modifications. The determination of the modifications of nucleic acids are of similar importance. This volume contains a discussion of the new tools emerging to study molecular composition and the structural details required to elucidate function of macromolecules individually and as assemblages ofc ommunicating molecular machines. Individual contributors describe their strategies for solving problems that represent all the major topics of biomedical significance in drug discovery, xiii PREFACE lipid mediators, protein characterization and expression (proteomics or functional and structural genomics), glycobiology, and structural variation and modification of nucleic acids affecting function. The participants and editors wish to acknowledge the outstanding organizational and managerial capabilities of Ms. Marilyn F. Schwartz for the success of the Fourth Symposium. The editors are indebted to the editorial talents of Ms. Candy Stoner for design and preparation ofthe final copy of this volume for publication. We also wish to acknowledge the financial support ofthe NIH NCRR Grant RR 01614 (to ALB). A. L. Burlingame Steven A. Carr Michael A. Baldwin xiv