| Download | - View accepted manuscript: Lactone-bound structures of cyclohexanone monooxygenase provide insight into the stereochemistry of catalysis (PDF, 682 KB)
|
|---|
| DOI | Resolve DOI: https://doi.org/10.1021/cb500442e |
|---|
| Author | Search for: Yachnin, Brahm J.; Search for: McEvoy, Michelle B.; Search for: Maccuish, Roderick J. D.; Search for: Morley, Krista L.1 ; Search for: Lau, Peter C. K.; Search for: Berghuis, Albert M. |
|---|
| Name affiliation | - National Research Council Canada. Aquatic and Crop Resource Development
|
|---|
| Format | Text |
|---|
| Type | Article |
|---|
| Journal title | ACS Chemical Biology |
|---|
| ISSN | 1554-8929 |
|---|
| Volume | 9 |
|---|
| Issue | 12 |
|---|
| Pages | 2843–2851; # of pages: 9 |
|---|
| Subject | cyclohexanone; enzyme; lactone; microbial enzyme; polycaprolactone; unspecific monooxygenase; binding site; catalysis; conformational transition; crystal structure; enzyme structure; oxidation; protein conformation; protein cross linking; stereochemistry; stereospecificity |
|---|
| Abstract | 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, 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 | 2014-09-29 |
|---|
| Publisher | ACS Publishing |
|---|
| Language | English |
|---|
| Peer reviewed | Yes |
|---|
| NRC number | NRC-ACRD-56113 |
|---|
| NPARC number | 21275605 |
|---|
| Export citation | Export as RIS |
|---|
| Report a correction | Report a correction |
|---|
Record identifier | 1e2b203d-281c-480e-8f7c-309ea82bfa26 | | Record created | 2015-07-14 |
|---|
| Record modified | 2016-05-09 |
|---|
