2FHS

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

2FHS の概要

• エントリーDOI: 10.2210/pdb2fhs/pdb
• 分子名称: enoyl-[acyl-carrier-protein] reductase, NADH-dependent, Acyl carrier protein (3 entities in total)
• 機能のキーワード: protein-protein complex, oxidoreductase-biosynthetic protein complex, oxidoreductase/biosynthetic protein
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Cytoplasm: P0A6A8
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 64431.31

構造登録者

Kolappan, S.,Novichenok, P.,Rafi, S.,Simmerling, C.,Tonge, P.J.,Kisker, C. (登録日: 2005-12-27, 公開日: 2006-10-17, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)