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Andrew D Mesecar

Biochemistry 

  • Head BCHM/Professor BCHM & BioSci/PCCR Deputy Director
765.494.1607
765.494.7897
BCHM Room 121A


Area of Expertise: Gene-to Lead Drug Discovery

The fundamental research interests of the Mesecar lab involve elucidating the molecular mechanisms and function of therapeutic enzymes and proteins.  We wish to understand at the molecular level how enzymes and proteins recognize their substrates, catalyze their requisite chemical reactions, and trigger signal-transduction cascades. Our ultimate goal is to utilize this fundamental scientific knowledge to develop new therapeutics to treat cancer and infectious diseases. 

To achieve these goals, we integrate a variety of state-of-the-art research tools and approaches including X-ray crystallography, enzyme chemistry and kinetics, molecular biology, bioinformatics, mass spectrometry, and computational chemistry to gain an understanding of the role of protein dynamics and conformational change in molecular recognition and catalysis. We then couple these technologies with high-throughput screening and structure-based design to develop compounds capable of modulating the activity of enzymes and receptors involved in cancer chemoprevention, cancer cell proliferation, cell longevity, and bacterial and viral pathogenesis.

Selected Publications

Conda-Sheridan, M., Marler, L., Park, E., Kondratyuk, T. P., Jermihov, K., Mesecar, A. D., . . . Cushman, M. S. (2010). Potential Chemopreventive Agents Based on the Structure of the LeadCompound 2-Bromo-1-hydroxyphenazine, Isolated from Streptomyces Species,Strain CNS284. JOURNAL OF MEDICINAL CHEMISTRY, 53(24), 8688-8699.

Small, E., Eggler, A., & Mesecar, A. D. (2010). "Development of efficient E. coli expression and purification system for a catalytically active, human Cullin3-RINGBox1 protein complex and elucidation of its quaternary structure with Deap1" Biochem Bio;hys Res Commun, 400, 471-475.

Wubben, T. J., & Mesecar, A. D. (2010). Kinetic, Thermodynamic, and Structural Insight into the Mechanism ofPhosphopantetheine Adenylyltransferase from Mycobacterium tuberculosis. JOURNAL OF MOLECULAR BIOLOGY, 404(2), 202-219.

Sun, B., Hoshino, J., Jermihov, K., Marler, L., Pezzuto, J. M., Mesecar, A. D., & Cushman, M. S. (2010). Design, synthesis, and biological evaluation of resveratrol analogues asaromatase and quinone reductase 2 inhibitors for chemoprevention ofcancer. BIOORGANIC & MEDICINAL CHEMISTRY, 18(14), 5352-5366.

Calamini, B., Ratia, K., Malkowski, M. G., Cuendet, M., Pezzuto, J. M., Santarsiero, B. D., & Mesecar, A. D. (2010). Pleiotropic mechanisms facilitated by resveratrol and its metabolites. BIOCHEMICAL JOURNAL, 429(2), 273-282.

Ghosh, A. K., Takayama, J., Rao, K. V., Ratia, K., Chaudhuri, R., Mulhearn, D. C., . . . Mesecar, A. D. (2010). Severe Acute Respiratory Syndrome Coronavirus Papain-like Novel ProteaseInhibitors: Design, Synthesis, Protein-Ligand X-ray Structure andBiological Evaluation. JOURNAL OF MEDICINAL CHEMISTRY, 53(13), 4968-4979.

Burks, E. A., Fleming, C. D., Mesecar, A. D., Whitman, C. P., & Pegan, S. D. (2010). Kinetic and Structural Characterization of a Heterohexamer4-Oxalocrotonate Tautomerase from Chloroflexus aurantiacus J-10-fl:Implications for Functional and Structural Diversity in the TautomeraseSuperfamily. BIOCHEMISTRY, 49(24), 5016-5027.

Clementz, M. A., Chen, Z., Banach, B. S., Wang, Y., Sun, L., Ratia, K., . . . Baker, S. C. (2010). Deubiquitinating and Interferon Antagonism Activities of CoronavirusPapain-Like Proteases. JOURNAL OF VIROLOGY, 84(9), 4619-4629.

Yang, J., Kondratyuk, T. P., Marler, L. E., Qiu, X., Choi, Y., Cao, H., . . . Zhang, H. (2010). Isolation and evaluation of kaempferol glycosides from the fernNeocheiropteris palmatopedata. PHYTOCHEMISTRY, 71(5-6), 641-647.

Pegan, S. D., Tian, Y., Sershon, V., & Mesecar, A. D. (2010). A Universal, Fully Automated High Throughput Screening Assay forPyrophosphate and Phosphate Release from Enzymatic Reactions. COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 13(1), 27-38.

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