2FHS

Structure of Acyl Carrier Protein Bound to FabI, the Enoyl Reductase from Escherichia Coli

Summary for 2FHS

• Entry DOI: 10.2210/pdb2fhs/pdb
• Descriptor: enoyl-[acyl-carrier-protein] reductase, NADH-dependent, Acyl carrier protein (3 entities in total)
• Functional Keywords: protein-protein complex, oxidoreductase-biosynthetic protein complex, oxidoreductase/biosynthetic protein
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm: P0A6A8
• Total number of polymer chains: 3
• Total formula weight: 64431.31

Authors

Kolappan, S.,Novichenok, P.,Rafi, S.,Simmerling, C.,Tonge, P.J.,Kisker, C. (deposition date: 2005-12-27, release date: 2006-10-17, Last modification date: 2024-02-14)

Primary citation

Rafi, S.,Novichenok, P.,Kolappan, S.,Zhang, X.,Stratton, C.F.,Rawat, R.,Kisker, C.,Simmerling, C.,Tonge, P.J.
Structure of Acyl Carrier Protein Bound to FabI, the FASII Enoyl Reductase from Escherichia coli.
J.Biol.Chem., 281:39285-39293, 2006

PubMed 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.

PubMed: 17012233
DOI: 10.1074/jbc.M608758200

Experimental method

X-RAY DIFFRACTION (2.7 Å)