2fhs
From Proteopedia
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Structure of Acyl Carrier Protein Bound to FabI, the Enoyl Reductase from Escherichia Coli
Overview
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.
About this Structure
2FHS is a Protein complex structure of sequences from Escherichia coli and Escherichia coli 042. Active as [acyl-carrier-protein_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number 1.3.1.9 Full crystallographic information is available from OCA.
Reference
Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli., Rafi S, Novichenok P, Kolappan S, Zhang X, Stratton CF, Rawat R, Kisker C, Simmerling C, Tonge PJ, J Biol Chem. 2006 Dec 22;281(51):39285-93. Epub 2006 Sep 29. PMID:17012233 [[Category: Enoyl-[acyl-carrier-protein] reductase (NADH)]]
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