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COLLOQUIUM ON PROTEOLYTIC PROCESSING AND PHYSIOLOGICAL REGULATION

NATIONAL ACADEMY OF SCIENCES
WASHINGTON, D.C. 1999



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Colloqium on Proteolytic Processing and Physiological Regulation COLLOQUIUM ON PROTEOLYTIC PROCESSING AND PHYSIOLOGICAL REGULATION NATIONAL ACADEMY OF SCIENCES WASHINGTON, D.C. 1999

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Colloqium on Proteolytic Processing and Physiological Regulation NATIONAL ACADEMY OF SCIENCES Colloquium Series In 1991, the National Academy of Sciences inaugurated a series of scientific colloquia, five or six of which are scheduled each year under the guidance of the NAS Council’s Committee on Scientific Programs. Each colloquium addresses a scientific topic of broad and topical interest, cutting across two or more of the traditional disciplines. Typically two days long, colloquia are international in scope and bring together leading scientists in the field. Papers from colloquia are published in the Proceedings of the National Academy of Sciences (PNAS).

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Colloqium on Proteolytic Processing and Physiological Regulation Proteolytic Processing and Physiological Regulation A Colloquium sponsored by the National Academy of Sciences February 20–21, 1999 PROGRAM Saturday, February 20, 1999 Hans Neurath, University of Washington Welcome and introduction: Proteolytic enzymes, past and future David Agard, University of California, San Francisco Kinetic stability and folding of proteases: twin paradigms for protease pro regions Michael James, University of Alberta Structural basis and mechanism of zymogen activation David Matthews, Agouron Pharmaceuticals, Inc. Structure-assisted design of mechanism based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes Christopher Walsh, Harvard University Role of D, D-Peptidase in Vancomycin Resistance Earl Davie, University of Washington Introduction to Protease activated receptors Shaun Coughlin, University of California, San Francisco Thrombin signaling: Molecular mechanisms and roles in vivo Vishva Dixit, Genentech, Inc. Identification of components of the cell death pathway Wolfram Bode, Max-Planck-Institute for Biochemistry Structure of tryptase, a cage-like serine proteinase involved in asthma, allergic and inflammatory disorders Philip Beachy, Johns Hopkins University Hedgehog protein biogenesis and signaling Marc Kirschner, Harvard University The role of proteases in the regulation of cell cycle

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Colloqium on Proteolytic Processing and Physiological Regulation Sunday, February 21, 1999 C.S.Craik, University of California, San Francisco Introduction Arthur Horwich, Yale University Chaperone Rings in Protein Folding and Degradation Robert Huber, Max-Planck-Institute for Biochemistry Structure of the archaeal and yeast 20S proteasomes and of the eubacterial Analog HslV Sukanto Sinha, Athena Neurosciences Cellular mechanism of beta amyloid production and secretion Michael Brown, University of Texas Southwestern Medical Center A proteolytic system that controls cholesterol metabolism Michael Brown Introduction Charles Craik, University of California, San Francisco Reverse biochemistry-using protease inhibitors to dissect complex biochemical processes Christine Debouck, Smith-Kline and Beecham Pharmaceuticals From genomics to drugs—cathepsin K and osteoporosis James McKerrow, University of California, San Francisco Parasite proteases—windows on molecular evolution and targets for drug design Joshua Boger, Vertex Pharmaceuticals Recognizing a drug

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Colloqium on Proteolytic Processing and Physiological Regulation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Table of Contents Papers from a National Academy of Sciences Colloquium on Proteolytic Processing and Physiological Regulation     Proteolytic enzymes, past and future Hans Neurath   10962–10963     Caspase activation: The induced-proximity model Guy S.Salvesen and Vishva M.Dixit   10964–10967     Structural aspects of activation pathways of aspartic protease zymogens and viral 3C protease precursors Amir R.Khan, Nina Khazanovich-Bernstein, Ernst M.Bergmann, and Michael N.G.James   10968–10975     The catalytic sites of 20S proteasomes and their role in subunit maturation: A mutational and crystallographic study Michael Groll, Wolfgang Heinemeyer, Sibylle Jäger, Tobias Ullrich, Matthias Bochtler, Dieter H.Wolf, and Robert Huber   10976–10983     The structure of the human ßII-tryptase tetramer: Fo(u)r better or worse Christian P.Sommerhoff, Wolfram Bode, Pedro J.B.Pereira, Milton T.Stubbs, Jörg Stürzebecher, Gerd P.Piechottka, Gabriele Matschiner, and Andreas Bergner   10984–10991     Sonic hedgehog protein signals not as a hydrolytic enzyme but as an apparent ligand for Patched Naoyuki Fuse, Tapan Maiti, Baolin Wang, Jeffery A.Porter, Traci M.Tanaka Hall, Daniel J.Leahy, and Philip A.Beachy   10992–10999     Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus serotypes D.A.Matthews, P.S.Dragovich, S.E.Webber, S.A.Fuhrman, A.K.Patick, L.S.Zalman, T.F.Hendrickson, R.A.Love, T.J.Prins, J.T.Marakovits, R.Zhou, J.Tikhe, C.E.Ford, J.W.Meador, R.A.Ferre, E.L.Brown, S.L.Binford, M.A.Brothers, D.M.DeLisle, and S.T.Worland   11000–11007     Kinetic stability as a mechanism for protease longevity Erin L.Cunningham, Sheila S.Jaswal, Julie L.Sohl, and David A.Agard   11008–11014     Cysteine protease inhibitors as chemotherapy: Lessons from a parasite target Paul M.Selzer, Sabine Pingel, Ivy Hsieh, Bernhard Ugele, Victor J.Chan, Juan C.Engel, Matthew Bogyo, David G.Russell, Judy A.Sakanari, and James H.McKerrow   11015–11022

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Colloqium on Proteolytic Processing and Physiological Regulation     How the protease thrombin talks to cells Shaun R.Coughlin   11023–11027     VanX, a bacterial D-alanyl-D-alanine dipeptidase: Resistance, immunity, or survival function? Ivan A.D.Lessard and Christopher T.Walsh   11028–11032     Chaperone rings in protein folding and degradation Arthur L.Horwich, Eilika U.Weber-Ban, and Daniel Finley   11033–11040     A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood Michael S.Brown and Joseph L.Goldstein   11041–11048     Cellular mechanisms of ß-amyloid production and secretion Sukanto Sinha and Ivan Lieberburg   11049–11053     Reverse biochemistry: Use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue Toshihiko Takeuchi, Marc A.Shuman, and Charles S.Craik   11054–11061

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Colloqium on Proteolytic Processing and Physiological Regulation National Academy of Sciences Colloquia Bound Reprints Available In 1991, the National Academy of Sciences (NAS) inaugurated a series of scientific colloquia, several of which are held each year under the auspices of the NAS Coun cil Committee on Scientific Programs. These colloquia address scientific topics of broad and topical interest that cut across two or more traditional disciplines. Typically two days long, these colloquia are international in scope and bring together leading scientists in the field. Papers presented at these colloquia are published in the Proceedings of the National Academy of Sciences (PNAS) and are available online (www.pnas.org). Because they have generated much interest, these papers are now available in the form of collected bound reprints, which may be ordered through the National Academy Press. Currently available are: Carbon Dioxide and Climate Change ($11) Held November 13–15, 1995 (Irvine, CA) Computational Biomolecular Science ($16) Held September 12–13, 1997 (Irvine, CA) Earthquake Prediction ($16) Held February 10–11, 1995 (Irvine, CA) Elliptic Curves and Modular Forms ($7) Held March 15–17, 1996 (Washington, DC) Genetic Engineering of Viruses and Viral Vectors ($21) Held June 9–11, 1996 (Irvine, CA) Genetics and the Origin of Species ($8) Held January 31-February 1, 1997 (Irvine, CA) Geology, Mineralogy, and Human Welfare ($11) Held November 8–9, 1998 (Irvine, CA) Neurobiology of Pain ($8) Held December 11–13, 1998 (Irvine, CA) Neuroimaging of Human Brain Function ($17) Held May 29–31, 1997 (Irvine, CA) Plants and Population: Is There Time? ($8) Held December 5–6, 1998 (Irvine, CA) Protecting Our Food Supply: The Value of Plant Genome Initiatives ($13) Held May 29–31, 1997 (Irvine, CA) Science, Technology, and the Economy ($12) Held November 20–22, 1995 (Irvine, CA) The Age of the Universe, Dark Matter, and Structure Formation ($13) Held March 21–23, 1997 (Irvine, CA) Papers from future colloquia will be available for purchase after they appear in PNAS. Shipping and Handling Charges: In the U.S. and Canada please add $4.50 for the first reprint ordered and $0.95 for each additional reprint. Ordering Information: Telephone orders will be accepted only when charged to VISA, MasterCard, or American Express accounts. To order, call toll-free 1–800–624–6242 or order online at www.nap.edu and receive a 20% discount.