title: Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway.
abstract: ZhuH is a priming ketosynthase that initiates the elongation of the polyketide chain in the biosynthetic pathway of a type II polyketide, R1128. The crystal structure of ZhuH in complex with the priming substrate acetyl-CoA reveals an extensive loop region at the dimer interface that appears to affect the selectivity for the primer unit. Acetyl-CoA is bound in a 20 A-long channel, which placed the acetyl group against the catalytic triad. Analysis of the primer unit binding site in ZhuH suggests that it can accommodate acyl chains that are two to four carbons long. Selectivity and primer unit size appear to involve the side chains of three residues on the loops close to the dimer interface that constitute the bottom of the substrate binding pocket.
authors.affiliation: Department of Biophysics and Biochemistry, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Hu
authors.initials: H
authors.lastname: Pan
authors.forename: Shiou chuan
authors.initials: Sc
authors.lastname: Tsai
authors.forename: Eric S
authors.initials: ES
authors.lastname: Meadows
authors.forename: Larry J W
authors.initials: LJ
authors.lastname: Miercke
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Keatinge-Clay
authors.forename: Joe
authors.initials: J
authors.lastname: O'Connell
authors.forename: Chaitan
authors.initials: C
authors.lastname: Khosla
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry; D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D019281:Dimerization; D004926:Escherichia coli / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
chemical_list: D009097:Multienzyme Complexes; D000105:Acetyl Coenzyme A