Title: Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli. | Journal: The Journal of biological chemistry. 2006 Dec;281(51):39285-39293 | Authors: Rafi S, Novichenok P, Kolappan S, Stratton CF, Rawat R, Kisker C, Simmerling C, Tonge PJ. | Abstract: Acyl carrier proteins play a central role in metabolism by transporting substrates in a wide variety of pathways including the biosynthesis of fatty acids and polyketides. However, despite their importance, there is a paucity of direct structural information concerning the interaction of ACPs with enzymes in these pathways. Here we report the structure of an acyl-ACP substrate bound to the Escherichia coli fatty acid biosynthesis enoyl reductase enzyme (FabI), based on a combination of x-ray crystallography and molecular dynamics simulation. The structural data are in agreement with kinetic studies on wild-type and mutant FabIs, and reveal that the complex is primarily stabilized by interactions between acidic residues in the ACP helix alpha2 and a patch of basic residues adjacent to the FabI substrate-binding loop. Unexpectedly, the acyl-pantetheine thioester carbonyl is not hydrogen-bonded to Tyr(156), a conserved component of the short chain alcohol dehydrogenase/reductase superfamily active site triad. FabI is a proven target for drug discovery and the present structure provides insight into the molecular determinants that regulate the interaction of ACPs with target proteins. | See full PubMed entry: http://www.ncbi.nlm.nih.gov/pubmed/17012233 |
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