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Publication Abstract from PubMed

The fungal type III polyketide synthase 2'-oxoalkylresorcylic acid synthase (ORAS) primes with a range of acyl-Coenzyme A thioesters (C4-C20) and extends using malonyl-Coenzyme A to produce pyrones, resorcinols, and resorcylic acids. To gain insight into this unusual substrate specificity and product profile, we have determined the crystal structures of ORAS to 1.75 A resolution, the Phe-252-->Gly site-directed mutant to 2.1 A resolution, and a binary complex of ORAS with eicosanoic acid to 2.0 A resolution. The structures reveal a distinct rearrangement of structural elements near the active site that allows accommodation of long-chain fatty acid esters and a reorientation of the gating mechanism that controls cyclization and polyketide chain length. The roles of these structural elements are further elucidated by characterization of various structure-based site-directed variants. These studies establish an unexpected plasticity to the PKS fold, unanticipated from structural studies of other members of this enzyme family.

Distinct structural elements dictate the specificity of the type III pentaketide synthase from Neurospora crassa.,Rubin-Pitel SB, Zhang H, Vu T, Brunzelle JS, Zhao H, Nair SK Chem Biol. 2008 Oct 20;15(10):1079-90. PMID:18940668^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.