Lactone-bound structures of cyclohexanone monooxygenase provide insight into the stereochemistry of catalysis

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DOIResolve DOI: http://doi.org/10.1021/cb500442e
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TypeArticle
Journal titleACS Chemical Biology
ISSN1554-8929
Volume9
Issue12
Pages28432851; # of pages: 9
Subjectcyclohexanone; enzyme; lactone; microbial enzyme; polycaprolactone; unspecific monooxygenase; binding site; catalysis; conformational transition; crystal structure; enzyme structure; oxidation; protein conformation; protein cross linking; stereochemistry; stereospecificity
AbstractThe 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, ε-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.
Publication date
PublisherACS Publishing
LanguageEnglish
AffiliationNational Research Council Canada; Aquatic and Crop Resource Development
Peer reviewedYes
NRC numberNRC-ACRD-56113
NPARC number21275605
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Record identifier1e2b203d-281c-480e-8f7c-309ea82bfa26
Record created2015-07-14
Record modified2016-05-09
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