Different Structural Origins of the Enantioselectivity of Haloalkane Dehalogenases toward Linear β‐Haloalkanes: Open–Solvated versus Occluded–Desolvated Active Sites. Issue 17 (23rd March 2017)

• Record Type: Journal Article
• Authors: Liskova, Veronika; Stepankova, Veronika; Bednar, David; Brezovsky, Jan; Prokop, Zbynek; Chaloupkova, Radka; Damborsky, Jiri
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 17(2017)
• Page Start: 4719
• Page End: 4723
• Publication Date: 2017-03-23
• Subjects: enantioselectivity -- enzyme catalysis -- enzymes -- molecular modeling -- protein engineering; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201611193
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The enzymatic enantiodiscrimination of linear β‐haloalkanes is difficult because the simple structures of the substrates prevent directional interactions. Herein we describe two distinct molecular mechanisms for the enantiodiscrimination of the β‐haloalkane 2‐bromopentane by haloalkane dehalogenases. Highly enantioselective DbjA has an open, solvent‐accessible active site, whereas the engineered enzyme DhaA31 has an occluded and less solvated cavity but shows similar enantioselectivity. The enantioselectivity of DhaA31 arises from steric hindrance imposed by two specific substitutions rather than hydration as in DbjA. Abstract : Two recipes for success : Two distinct mechanisms are described for the enantiodiscrimination of 2‐bromopentane by haloalkane dehalogenases. Highly enantioselective DbjA has a very open, solvent‐accessible active site. The engineered enzyme DhaA31 has a more occluded and less solvated cavity (see picture) but shows similar enantioselectivity as a result of steric hindrance imposed by two specific residues, rather than hydration as in DbjA.