Andrew D. MesecarWalther Professor of Cancer Structural Biology—Biochemistry(Courtesy)
Office: HOCK 311
For Professor Mesecar's individual Home Page click here.
The main interest of the Mesecar lab is the Structure & Function of Enzymes of biomedical importance. One of our fundamental goals is to gain a deeper understanding into the roles of protein dynamics and conformational changes in the molecular recognition and catalytic processes and to exploit this knowledge for the design of small molecule drugs that target these enzymes.
We are currently studying the structure and function of enzymes involved in cancer chemoprevention, cancer cell proliferation and bacterial and viral pathogenesis. We are actively involved in the discovery of both natural and synthetic compounds that can be used as anti-cancer, anti-viral and anti-bacterial therapeutics, as well as compounds that can prevent cancer and promote cell longevity.
Due to the complex nature of enzymatic catalysis and molecular recognition, we routinely use a variety of state-of-the-art experimental approaches and tools from the fields of chemistry, biology and physics. Our main experimental tools are static and time-resolved X-ray crystallography, enzyme chemistry & kinetics, molecular biology, mass-spec proteomics, assay development and optimization, high-throughput screening and molecular modeling and cheminformatics. Our multi-faceted, multi-disciplinary, and integrated approach to the elucidation of the nature of enzymatic catalysis and molecular recognition is deemed to be the emerging model for scientific investigation and education in the twenty-first century.
Our current projects in the lab include: (1) the roles of deubiquitinating enzymes (DUBs) in cancer and antagonism of the innate immune response and targeting DUBs for anti-cancer and antiviral drug development; (2) regulation of the Keap1-Cul3-Rbx1 E3 Ubiquitin ligase system in regulating the cellular concentrations of the transcription factor Nrf2 and hence activation of the anti-oxidant response element (ARE); (3) the structure, function and evolution of coronavirus papain-like and 3C proteases and developing therapeutics targeted at these enzymes; and (4) determining the structure and mechanisms of bacterial (e.g. tuberculosis and anthrax) adenylyltrasferase enzymes in the CoA, NAD, FAD and menaquinone biosynthesis and evaluating these enzymes as potential drug targets.
EducationBS in Chemistry (ACS), 1988, Purdue University; Ph.D. in Biochemistry, 1995, University of Notre Dame; Post-Doctorate, 1995-1998, University of California, Berkeley
- Defense Science Study Group - U.S. Department of Defense, 2006-2008
- American Association of Colleges of Pharmacy New Investigator Award, 1999–2000
- U.S. Department of Energy: Post-Doctoral Fellowship Center for Advanced Materials, Lawrence Berkeley National Laboratory, 1995–1998
- Reilly Graduate Fellowship: University of Notre Dame, 1993–1994
- U.S. Department of Education: Graduate Fellowship. GAANNP Scholarship Program, 1989–1992
- U.S. Air Force ROTC Four-Year Scholarship, 1984
- Wubben TJ, Mesecar AD., Kinetic, thermodynamic, and structural insight into the mechanism of phosphopantetheine adenylyltransferase from Mycobacteriumtuberculosis. . J Mol Biol 2010 , 404(2), 202-19.
- Ratia K, Pegan S, Takayama J, Sleeman K, Coughlin M, Baliji S, Chaudhuri R, Fu W, Prabhakar BS, Johnson ME, Baker SC, Ghosh AK, Mesecar AD., A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication.. Proc Natl Acad Sci USA 2008 , 105(42), 16119-24.
- Ratia K, Saikatendu KS, Santarsiero BD, Barretto N, Baker SC, Stevens RC, Mesecar AD., Severe acute respiratory syndrome coronavirus papain-like protease: structure of a viral deubiquitinating enzyme. . Proc Natl Acad Sci USA 2006 , 103(15), 5717-22.