Download MendeleyCrystal structure of beta-ketoacyl-acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis.
Qiu, X., Janson, C.A., Konstantinidis, A.K., Nwagwu, S., Silverman, C., Smith, W.W., Khandekar, S., Lonsdale, J., Abdel-Meguid, S.S.(1999) J Biol Chem 274: 36465-36471
- PubMed: 10593943
- DOI: https://doi.org/10.1074/jbc.274.51.36465
- Primary Citation of Related Structures:
1HN9 - PubMed Abstract:
Beta-ketoacyl-acyl carrier protein synthase III (FabH), the most divergent member of the family of condensing enzymes, is a key catalyst in bacterial fatty acid biosynthesis and a promising target for novel antibiotics. We report here the crystal structures of FabH determined in the presence and absence of acetyl-CoA. These structures display a fold that is common for condensing enzymes. The observed acetylation of Cys(112) proves its catalytic role and clearly defines the primer binding pocket. Modeling based on a bound CoA molecule suggests catalytic roles for His(244) and Asn(274). The structures provide the molecular basis for FabH substrate specificity and reaction mechanism and are important for structure-based design of novel antibiotics.
Organizational Affiliation:
SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA. xiayang_qiu-1@sbphrd.com
