CRAIK, CHARLES S. / Medicine / Researchers

International Center for Scientific Research

Researchers

Medicine / CRAIK, CHARLES S.

craikcgl.ucsf.edu

Position

Professor in the Departments of Pharmaceutical Chemistry; Cellular and Molecular Pharmacology, and Biochemistry and Biophysics at the University of California at San Francisco.

Research interests

Proteolytic Enzymes Mediating Biological Function

Proteases are directly or indirectly involved in virtually every biological function or dysfunction. The omnipresence of proteases and their natural inhibitors has placed them among the most studied proteins in biochemistry. The research efforts of the lab focus primarily on the structure-function analysis of proteases and their inhibitors using a combination of genetic, biochemical and biophysical methods. Chemical biological approaches are used or are being developed to study the substrate specificity, catalytic mechanism and biological role of proteases and their macromolecular inhibitors. The genes for serine (trypsin, serine collagenase, easter, prostate specific antigen, T-cell specific granzymes, MT-SP1 and 2, KSHV protease), cysteine (cruzain, falcipain and SARS protease) and aspartyl (HIV1 & HIV2 & SIV) proteases and macromolecular inhibitors such as ecotin and single chain antibodies are manipulated and expressed in heterologous expression systems. Targeted, region specific or random substitutions are introduced recombinantly to create variants that provide insight into the structure and activity of the target protein. A particular emphasis of our work is on identifying the roles and regulating the activity of proteases associated with infectious diseases, cancer and development. These studies are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins. This in turn is leading to the development of strategies for regulating proteolytic activity as a means of therapeutic intervention. Further study of these proteins holds promise for better understanding, rapid detection and eventual control of infectious diseases and cancer.

Prizes and awards

National Honor Society; Alden Scholar, 1972-75

Doane Distinguished Scholar, Phi Beta Kappa, 1974-75

Richard Edwin Lee Scholar, 1975

Member, The Amer. Chem. Soc.; The Amer. Assoc. for the Advan. of Science, 1978

American Cancer Society Postdoctoral Fellow, 1982-83

NIH Postdoctoral Fellow, 1983-84

Member, American Society of Biological Chemists, 1983

Top 100 Innovators - Science Digest, 1985-86

Editorial Board Member of BioTechniques, 1987

Editorial Board Member of DNA, 1988

Associate Editor of Protein Engineering, 1988

Nominating Committee for The Protein Society, Member, The Protein Society, 1989-90

National Science Foundation Molecular Biochemistry Advisory Panel, 1993-96

Vice Chair of Gordon Conference on Proteolytic Enzymes and Inhibitors, 1996

Chairman of Gordon Conference on Proteolytic Enzymes and Inhibitors, 1998

Co-organizer of the Cold Spring Harbor Meeting on the Biology of Proteolysis, 1997, 1999, 2001

Publications

Lytic Replication of KaposiÕs Sarcoma-Associated Herpesvirus results in the Formation of Multiple Capsid Species: Isolation and Molecular Characterization of A, B, and C Capsids from a Gammaherpesvirus. K. Nealon, W. W. Newcomb, T.R. Pray, C.S. Craik, J.C. Brown and D.H. Kedes. J. Virol. 75, 2866-78 (2001)

Novel Inter-Protein Cross-link Identified in the GGH-ecotin D137Y Dimer. M. Person, K. Brown, S. Mahrus, C.S. Craik and A. Burlingame. Protein Science, 10, 1549-1562 (2001)

The Role of Ecotin Dimerization in Protease Inhibition. C. Eggers, S. Wang, R. J. Fletterick and C. S. Craik. J. Mol. Bio. 308, 975-991 (2001)

Definition of the Extended Substrate Specificity Determinants for Beta-Tryptases I and II. J.L. Harris, A. Niles, K. Burdick, M. Maffitt, B.J. Backus, J.A. Ellman, I. Kuntz, M. Haak-Frendscho, C.S. Craik, J. Bio. Chem., 276 (37), 34941-34947 (2001)

Structural Features of a Snake Venom Thrombin-like Enzyme: Thrombin and Trypsin on a Single Catalytic Platform. H.C. Castro, D.M. Silva, C.S. Craik, R.B. Zingali. Biochim Biophys Acta 1547, 183-95 (2001)

Altered Substrate Specificity of Drug-Resistant HIV-1 Protease. D. Dauber, R. Zierman, N. Parkin, D.J. Maly, S. Mahrus, J.L. Harris, J.A. Ellman, C. Petropoulos, C.S. Craik. J. Virol. 76, 1359-1368 (2002)

Conformational Change Coupling the Dimerization and Activation of KSHV Protease. T.R. Pray, K.K. Reiling, B.G. Dermirjian, C.S. Craik. Biochemistry 41(5), 1474-82 (2002)

Expedient Solid-Phase Synthesis of Fluorogenic Protease Substrates Using the 7-Amino-4-Carbamoylmethylcoumarin (ACC) Fluorophore. D.J. Maly, F. Leonetti, B.J. Backes, D.S. Dauber, J.L. Harris, C.S. Craik and J.A. Ellman. J. Org. Chem. 67(3), 910-915 (2002)

Chemically Mediated Site-specific Proteolysis. Alteration of Protein-Protein Interaction. B. Wang, K.C. Brown, M. Lodder, C.S. Craik, S.M. Hecht. Biochemistry 41 (8), 2805-2813 (2002)

Substrate Specificity of Schistosome Versus Human Legumain Determined by P1-P3 Peptide Libraries. M.A. Mathieu, M. Boygo, C.R. Caffrey, Y. Choe, J. Lee, H. Chapman, M. Sajid, C.S. Craik & J. McKerrow. Mol. Biochem. Parisitol 121 (1), 99-105 (2002)

Anisotropic Dynamics of the JE-2147-HIV Protease Complex: Drug Resistance and Thermodynamic Binding Mode Examined in a 1.09 structure. K.K. Reiling, N.F. Endres, D.S. Dauber, C.S. Craik, R.M. Stroud. Biochemistry 41(14), 4582-4594 (2002)

Computer-Assisted Mutagenesis of Ecotin to Engineer its Secondary Binding Site for Urokinase Inhibition. M.C. Laboissiere, M.M. Young, R.G. Pinho, S. Todd, R.J. Fletterick, I. Kuntz, C.S. Craik. J Bio. Chem. 277 (29), 26623-31 (2002)

Special Delivery (Letter to the Editor). C. Berry, B.M. Dunn, C.S. Craik and John Kay. Biochem & Mol. Bio. Education, 30(3), 151. (2002)

Selective Inhibition of the Collagenolytic Activity of Human Cathepsin K by Altering its S2 Subsite Specificity. F. LeCaille, Y. Choe, W. Brandt, Z. Li, C.S. Craik and Bromme D. Biochemistry 41(26), 8447-54 (2002)

Scanning the Prime-Site Substrate Specificity of Proteolytic Enzymes: A Novel Assay Based on Ligand-Enhanced lanthanide Ion Fluorescence. A. Barrios and C.S. Craik. Bioorg Med Chem Ltrs. 12(24), 3619-23 (2002)

Cercarial Elastase is Encoded by a Functionally Conserved Gene Family Across Multiple Species of Schistosomes. J.P. Salter, Y. Choe, H. Albrecht, C. Franklin, K.C. Lim, C.S. Craik, J.H. McKerrow. J. Bio. Chem. 277(27), 24618-24 (2002)

Critical Role of Amino Acid 23 in Mediating Activity and Specificity of Vickepain-2, a Papain-family Cystein Protease of Rodent Malaria Parasites. A. Singh, B.R. Shenai, Y. Choe, J. Gut, P.S. Sijwali, C.S. Craik and P.J. Rosenthal. Biochem J. 368(1), 273-81 (2002)

Design and Synthesis of Novel Inhibitors of Gelatinase B. X. Wang, Y. Choe C.S. Craik and J.A. Ellman. Bioorg & Med. Chem. Ltrs. 12(16), 2201-4 (2002)

Potent and Selective Inhibition of Membrane Type Serine Protease1 by Human Single-Chain Antibodies. J. Sun, J. Pons and C.S. Craik. Biochemistry (2002)

Quantitation of Membrane Type Serine Protease 1 (MT-SP1) in Transformed and Normal Cells. A.S. Bhatt, T. Takeuchi, B. Ylstra, D. Ginzinger, D. Albertson, M.A. Shuman and C.S. Craik. Biological Chemistry (2002)

Catalytic Properties and Inhibition of Proline-Specific Dipeptidyl Peptidases II, IV and VII. B. Leiting, K.D. Pryor, J.K. Wu, F. Marsilio, R.A. Patel, C.S. Craik, J.A. Ellman, R.T. Cummings and N. Thornberry. Biochemistry (2003)

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