4rg3

Publication Abstract from PubMed

The Baeyer-Villiger monooxygenases (BVMOs) are microbial enzymes that catalyze the synthetically useful Baeyer-Villiger oxidation reaction. The available BVMO crystal structures all lack a substrate or product bound in a position that would determine the substrate specificity and stereospecificity of the enzyme. Here, we report two crystal structures of cyclohexanone monooxygenase (CHMO) with its product, epsilon-caprolactone, bound: the CHMOTight and CHMOLoose structures. The CHMOTight structure represents the enzyme state in which substrate acceptance and stereospecificity is determined, providing a foundation for engineering BVMOs with altered substrate spectra and/or stereospecificity. The CHMOLoose structure is the first structure where the product is solvent accessible. This structure represents the enzyme state upon binding and release of the substrate and product. In addition, the role of the invariant Arg329 in chaperoning the substrate/product during the catalytic cycle is highlighted. Overall, these data provide a structural framework for the engineering of BVMOs with altered substrate spectra and/or stereospecificity.

Lactone-bound structures of cyclohexanone monooxygenase provide insight into the stereochemistry of catalysis.,Yachnin BJ, McEvoy MB, MacCuish RJ, Morley KL, Lau PC, Berghuis AM ACS Chem Biol. 2014 Sep 29. PMID:25265531^[1]

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