Charles Craik

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Charles Craik

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Professor, School of Pharmacy
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My research interests focus on defining the roles and the mechanisms of enzymes and other challenging proteins in complex biological processes and on developing technologies to facilitate these studies. The current research in the Craik lab focuses on the chemical biology of proteolytic and protein degradation enzymes, receptors and membrane transporters. A particular emphasis of our work is on identifying the roles and regulating the activity of key proteins associated with infectious diseases, neurodegeneration and cancer. I am also interested in developing novel methods to biophysically characterize challenging proteins as well as their complexes. These studies coupled with our global substrate profiling, antibody engineering and noninvasive imaging efforts are providing a better understanding of both the chemical make-up and the biological importance of these critical proteins to aid in the rapid detection, monitoring and control of infectious disease, neurological disorders and cancer. This in turn is leading to the development of strategies for regulating these activities as a means of therapeutic intervention. Further study of these proteins holds promise for better understanding, rapid detection and eventual control of infectious diseases, cancer and neurodegeneration.
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  1. Perona JJ, Craik CS, Fletterick RJ. Locating the catalytic water molecule in serine proteases. Science. 1993 Jul 30; 261(5121):620-2.
  2. Corey DR, Shiau AK, Yang Q, Janowski BA, Craik CS. Trypsin display on the surface of bacteriophage. Gene. 1993 Jun 15; 128(1):129-34.
  3. C.S.Craik. Modus Operandi. Nature . 1991; 353, 469 .
  4. Eakin AE, McGrath ME, McKerrow JH, Fletterick RJ, Craik CS. Production of crystallizable cruzain, the major cysteine protease from Trypanosoma cruzi. J Biol Chem. 1993 Mar 25; 268(9):6115-8.
  5. McGrath ME, Haymore BL, Summers NL, Craik CS, Fletterick RJ. Structure of an engineered, metal-actuated switch in trypsin. Biochemistry. 1993 Mar 02; 32(8):1914-9.
  6. Z. Sui, J. DeVoss, D. DeCamp, J. Li, C.S. Craik & P.R. Ortiz de Montellano. Synthesis. Synthesis of Haloperidol Ethanedithioketal HIV-1 Protease Inhibitors: Magnesium Chloride Facilitated Addition of Grignard Reagents. 1993; 8:803-808.
  7. E. Rutenber, E.B. Fauman, R.J. Keenan, S. Fong, P.S. Furth, P.R. Ortiz de Montellano, E. Meng, I.D. Kuntz, D.L. DeCamp, R. Salto, J.R. Rosé, C.S. Craik, R.M. Stroud. . J. Bio. Chem. Structure of a Non-Peptide Inhibitor Complexed with HIV-1 Protease: Developing a Cycle of Structure-Based Drug Design. 1993; 15343-15346.
  8. D.L. Decamp, S.B. Kahl & C.S. Craik. Boronated Porphyrins—A New Class of HIV Proteinase Inhibitors. Intl. Antiviral News 1. 1993; 19-20 .
  9. J.J. Perona, C.A. Tsu, M.E. McGrath, C.S. Craik & R.J. Fletterick. Relocating a Negative Charge in the Binding Pocket of Trypsin. J. Mol. Bio. 230. 1993; 934-949.
  10. T.K. Sawyer, J.F. Fisher, J.B. Hester, C.W. Smith, A.G. Tomasselli, W.G. Tarpley, P.S. Burton, J.O. Hui T.J. McQuade, R.A. Conradi, V.S. Bradford, L. Liu, J.H. Kinner, J.Tustin,D.L. Alexander, A.W. Harrison, D.E. Emmert, D.J. Staples, L.I. Maggira, Y.Z. Zhang, R.A. Poorman, BM. Dunn, C. Rao, .E. Scarborough, W.T. Lowther, C.S. Craik, D. DeCamp, J.Moon, W.H. Howe & R.L. Heinrikson. Peptidomimetic Inhibitors of Human Immunodeficiency Virus Protease (HIV-PR): Design, Enzyme Binding and Selectivity, Antiviral Efficacy and Cell Permeability Properties. Bioorg. Med. Chem. Letts 3. 1993; 819-824 .
  11. Z. Sui, R. Salto, C.S. Craik, P. Ortiz de Montellano. Inhibition of the HIV1 and the HIV2 Proteases by Curcumin and Curcumin Boron Complexes. Bioorg. & Med. Chem. Let. 1 . 1993; 415-422 .
  12. Babé LM, Rosé J, Craik CS. Synthetic "interface" peptides alter dimeric assembly of the HIV 1 and 2 proteases. Protein Sci. 1992 Oct; 1(10):1244-53.
  13. Higaki JN, Fletterick RJ, Craik CS. Engineered metalloregulation in enzymes. Trends Biochem Sci. 1992 Mar; 17(3):100-4.
  14. L. Evnin, J. Vasquez & C.S. Craik. Proc. Substrate Specificity of Trypsin Investigated Using a Genetic Selection. Natl. Acad. Sci. USA 87 . 1990; 6659-6663.
  15. A.L. Ferris, A. Hizi, S.D. Showalter, S. Pichuantes, L. Babé & C.S. Craik. Immunologic and Proteolytic Analysis of HIV-2 Reverse Transcriptase Structure. Virology 175. 1990; 456-464 .
  16. E. Stewart, C.S. Craik, L. Hake & A. Bowcock. Human CPA Identifies a BglII RFLP and Maps to 7q31-qter. Amer. J. Hum. Gen. 46, 795 -800 . 1990.
  17. M. Obukowicz, M. Gustafson, K. Junger, R. Leimgruber, A. Wittwer, T-C. Wun, T. Warren, B. Bishop, K. Mathis, D. McPherson, N. Siegel, M. Jennings, B. Brightwell, J. Diaz-Collier, L. Bell, C.S. Craik & W. Tacon. Secretion of Active Kringle 2-Serine Protease in E. coli. J. Bio. Chem. 29, 9737-9745 . 1990.
  18. S. Pichuantes, L. Babé, P. Barr, D. DeCamp & C.S. Craik. Recombinant HIV 2 Protease Processes HIV 1 Pr53gag and Analogous Junction Peptides In Vitro. J. Bio. Chem. 265, 13890-13898 . 1990.
  19. D.R. Corey, M.E. McGrath, J.R. Vasquez, R.J. Fletterick & C.S. Craik. An Alternate Geometry for the Catalytic Triad of Serine Proteases. J. Amer. Chem. Soc. 114. 1992; 4906-4907 .
  20. Sloane DL, Leung R, Craik CS, Sigal E. A primary determinant for lipoxygenase positional specificity. Nature. 1991 Nov 14; 354(6349):149-52.
  21. Wilke ME, Higaki JN, Craik CS, Fletterick RJ. Crystal structure of rat trypsin-S195C at -150 degrees C. Analysis of low activity of recombinant and semisynthetic thiol proteases. J Mol Biol. 1991 Jun 05; 219(3):511-23.
  22. Babé LM, Pichuantes S, Craik CS. Inhibition of HIV protease activity by heterodimer formation. Biochemistry. 1991 Jan 08; 30(1):106-11.
  23. Wilke ME, Higaki JN, Craik CS, Fletterick RJ. Crystallographic analysis of trypsin-G226A. A specificity pocket mutant of rat trypsin with altered binding and catalysis. J Mol Biol. 1991 Jun 05; 219(3):525-32.
  24. McGrath ME, Hines WM, Sakanari JA, Fletterick RJ, Craik CS. The sequence and reactive site of ecotin. A general inhibitor of pancreatic serine proteases from Escherichia coli. J Biol Chem. 1991 Apr 05; 266(10):6620-5.
  25. Earnest T, Fauman E, Craik CS, Stroud R. 1.59 A structure of trypsin at 120 K: comparison of low temperature and room temperature structures. Proteins. 1991; 10(3):171-87.