Michael Garavito
R. Michael Garavito
Professor
  • B.A. 1974, University of California, San Diego
  • Ph.D. 1978, Purdue University
  • Postdoctoral Fellow, 1979-82, Biocenter, University of Basel, Switzerland
  • Independent Scientist, 1983-86, Biocenter, University of Basel, Switzerland
  • Faculty Member, 1987-95, University of Chicago
garavito@msu.edu
513 Biochemistry Building
Michigan State University
East Lansing, MI 48824-1319
Office: 517-355-9724
Lab: 517-353-9125
FAX: 517-353-9334

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R. Michael Garavito

Research Interests

My research involves the elucidation of structure-function relationships in membrane proteins and molecular complexes using macromolecular crystallography and other biophysical methods. I have focused a significant portion of my research efforts on the development of crystallization methods for membrane proteins and the study of membrane protein structure and function. The research on prostaglandin H synthase (PGHS) and mammalian hexokinases (HKs) are two of the membrane protein projects in the laboratory. My group is also pursuing research into the structure and function of several enzymes involved in the biosynthesis of glycolipids and glycosteroids.

Prostaglandin endoperoxide H synthases-1 and -2 (PGHS-1 and -2) are heme-containing, integral membrane proteins which catalyze the committed step in the biosynthesis of prostaglandins, a large group of bioactive, oxygenated C18-C22 compounds. PGHS-1 and -2 convert arachidonic acid to prostaglandin H2, via the cyclooxygenase (COX) and peroxidase (POX) reactions. Prostaglandin H2 is then converted by specific synthases into bioactive prostaglandins and thromboxanes. The understanding the structure and function of the PGHS isozymes has been the focus of much research because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) which include the "over-the-counter" drugs aspirin and ibuprofen. The PGHS isozymes have been implicated in the pathophysiology of arthritis (inflammation and free radical damage), cardiovascular disease, cancer (tumor production, metastasis and carcinogen activation), and various neurological disorders like Alzheimer's and Parkinson's diseases. NSAIDs are already used to treat symptoms of inflammatory and cardiovascular disease. Knowledge of the structure of these enzymes is a prerequisite for understanding how to improve our ability to control the activity of PGHS isozymes through drug therapy.spectroscopy.MORE

Recent Publications

Jadhav SR, Sui D, Garavito RM, Worden RM. (2008) Fabrication of highly insulating tethered bilayer lipid membrane using yeast cell membrane fractions for measuring ion channel activity. J Colloid Interface Sci. Jun 15;322(2):465-72.

Lin, H. J., Levine, A. J., Materi, A. M., Park, J. M., Patterson, R. E., Goodmand, J. E., Chlebowski, R. T., Sansbury, L. B., Kekug, T. O., Henderson, B. E., Kolonel, L. N., Le Marchand, L., Harris, C. C., Sandler, R. S., Haile, R. W., Garavito, R. M., Lawson, J. A., and Kapoor, S. (2007) "Prostaglandin H synthase 2 (PTGS2, or Cox-2) Val511Ala variant in African Americans: pooled analyses of four case-control studies of colorectal cancer and measurements of prostaglandin synthesis and excretion in vivo." Prostaglandins, Leukotrienes and Essential Fatty Acids, in press.

Wada M, DeLong CJ, Hong YH, Rieke CJ, Song I, Sidhu RS, Yuan C, Warnock M, Schmaier AH, Yokoyama C, Smyth EM, Wilson SJ, FitzGerald GA, Garavito RM, Sui de X, Regan JW, Smith WL. (2007) Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem. 3;282(31):22254-66.

Harman CA, Turman MV, Kozak KR, Marnett LJ, Smith WL, Garavito RM. (2007) Structural basis of enantioselective inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides. J Biol Chem. 21;282(38):28096-105.

Qin L, Sharpe MA, Garavito RM, Ferguson-Miller S. (2007) Conserved lipid-binding sites in membrane proteins: a focus on cytochrome c oxidase. Curr Opin Struct Biol. 17(4):444-50.

Qin L, Mills DA, Hiser C, Murphree A, Garavito RM, Ferguson-Miller S, Hosler J. (2007) Crystallographic location and mutational analysis of Zn and Cd inhibitory sites and role of lipidic carboxylates in rescuing proton path mutants in cytochrome c oxidase. Biochemistry. 29;46(21):6239-48.

Powers R. A., C. L. Rife, A. L. Schilmiller, G. A. Howe, and R. M. Garavito (2006) Structure determination and analysis of acyl-CoA oxidase (ACX1) from tomato. Acta Cryst. D62, 683-86.

Qin, L., C. Hiser, A. M. Mulichak, R. M. Garavito, and S. Ferguson-Miller. (2006) Crystal Structure at 2.0 Å Resolution of the Catalytic Core of Cytochrome c Oxidase and Identification of Conserved Lipid Binding Sites. Proc. Natl. Acad. Sci. 103, 16117-22. MORE