Substrate recognition by bacterial enoyl reductases

BIOL 91

Xujie Zhang, xuzhang@ic.sunysb.edu, Department of chemistry, SUNY-stony brook, 97 Nicollos road, Room 635, Department of Chemistry, SUNY-SB, stony brook, NY 11790 and Peter J Tonge, Institute of Chemical Biology & Drug Discovery and Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400.
Tuberculosis (TB) kills over two million people every year. We are currently studying a series of known or putative enzyme drug targets from MTB that includes InhA, the NADH-dependent enoyl-ACP reductase from the MTB fatty acid biosynthesis (FASII) pathway. InhA is a validated target for drug discovery and we are investigating the interaction with the natural acyl carrier protein substrate (AcpM). Based on studies with the E. coli enoyl reductase homologue, we hypothesized that three basic residues close to the substrate binding loop in InhA, R195, R225, and K233, interact with acidic residues in the AcpM recognition helix. We also have evidence that an additional set of basic residues close to AcpM Helix II, R45, R49, R53, play a critical role in AcpM recognition by InhA.Our studies also have implications for the ability of acyl carrier protein to recognize and interact with a diverse array of intracellular protein targets.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007