Faculty Lecture Series


When

Wednesday, March 10, 2010
5 PM - 6 PM

Where

Valerie Timken Amphitheater
Green Hospital

Who

Benjamin F. Cravatt, Ph.D.
Professor and Chair, Department of Chemical Physiology
Investigator, Dorris Neuroscience Center
Member, Skaggs Institute for Chemical Biology

Topic

"Activity-based proteomics and its application for enzyme and inhibitor discovery"
  Genome sequencing projects have revealed that eukaryotic and prokaryotic organisms universally possess a huge number of uncharacterized enzymes. The functional annotation of enzymatic pathways thus represents a grand challenge for researchers in the post-genomic era. To address this problem, we have introduced chemical proteomic and metabolomic technologies that globally profile enzyme activities in complex biological systems. These methods include activity-based protein profiling (ABPP), which utilizes active site-directed chemical probes to determine the functional state of large numbers of enzymes in native proteomes. In this lecture, I will describe the integrated application of ABPP and complementary metabolomic methods to discover and functionally annotate enzyme activities in mammalian (patho)physiological processes, including neurotransmitter metabolism and cancer malignancy. I will also present competitive ABPP platforms for developing selective inhibitors of enzymes and discuss ongoing challenges that face researchers interested in assigning protein function using chemoproteomic methods.

Selected Publications

  Nomura, D.K., J.Z. Long, S. Niessen, H.S., Hoover, S. Ng, B.F. Cravatt. 2010. Monoacylglycerol Lipase Regulates a Fatty Acid Network that Promotes Cancer Pathogenesis. Cell 140:49-61.
  Bachovchin, D.A., S.J. Brown, H. Rosen, B.F. Cravatt. 2009. Identification of selective inhibitors of uncharacterized enzymes by high-throughput screening with fluorescent activity-based probes. Nat. Biotechnol. 27:387-94.
  Long, J.Z., W. Li, L. Booker, J.J. Burston, S.H. Kinsey, J.E. Schlosburg, F.J. Pavon, A.M. Serrano, D.E. Selley, L.H. Parsons, A.H. Lichtman, B.F. Cravatt. 2009. Selective blockade of 2-arachidonoylglycerol hydrolysis produces cannabinoid behavioral effects. Nat. Chem. Biol. 5:37-44.
  Cravatt, B.F., A.T. Wright, J.W. Kozarich. 2008. Activity-based protein profiling: from enzyme chemistry to proteomic chemistry. Annu. Rev. Biochem. 77:383-414.
  Jessani, N., S. Niessen, B.Q. Wei, M. Nicolau, M. Humphrey, Y. Ji, W. Han, D.Y. Noh, J.R. Yates, S.S. Jeffrey, B.F. Cravatt. 2005. A streamlined platform for high-content functional proteomics of primary human specimens. Nat Methods. 2:691-697.