Download MendeleyRefined structures of beta-ketoacyl-acyl carrier protein synthase III.
Qiu, X., Janson, C.A., Smith, W.W., Head, M., Lonsdale, J., Konstantinidis, A.K.(2001) J Mol Biol 307: 341-356
- PubMed: 11243824
- DOI: https://doi.org/10.1006/jmbi.2000.4457
- Primary Citation of Related Structures:
1HND, 1HNH, 1HNJ, 1HNK - PubMed Abstract:
beta-Ketoacyl-acyl carrier protein synthase III (FabH) is a condensing enzyme that plays central roles in fatty acid biosynthesis. Three-dimensional structures of E. coli FabH in the presence and absence of ligands have been refined to 1.46 A resolution. The structures of improved accuracy revealed detailed interactions involved in ligand binding. These structures also provided new insights into the FabH mechanism, e.g. the possible role of a water or hydroxyl anion in Cys112 deprotonation. A structure of the apo enzyme uncovered large conformational changes in the active site, exemplified by the disordering of four essential loops (84-86, 146-152, 185-217 and 305-307) and the movement of catalytic residues (Cys112 and His244). The disordering of the loops leads to greater than 50 % reduction in the FabH dimer interface, suggesting a dynamic nature for an unusually large portion of the dimer interface. The existence of a large solvent-accessible channel in the dimer interface as well as two cis-peptides (cis-Pro88 and cis-Phe308) in two of the disordered loops may explain the observed structural instabilities.
Organizational Affiliation:
Department of Structural Biology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA. [email protected]
