title: Inverting the enantioselectivity of a carbonyl reductase via substrate-enzyme docking-guided point mutation.
abstract: Substrate-enzyme docking-guided point mutation of a carbonyl reductase from Sporobolomyces salmonicolor led to mutant enzymes, which reversed the enantiopreference and enhanced the enantioselectivity toward the reduction of para-substituted acetophenones. Such a dramatic change in the enantioselectivity indicates that the 245 residue in the catalytic site plays a critical role in determining the enantioselectivity of these ketone reductions, providing valuable insight into our understanding of how residues involved in substrate binding affect the orientation of bound substrate and thus control the reduction stereoselectivity.
authors.affiliation: Department of Chemistry, Southern Methodist University, Dallas, Texas 75275, USA. dzhu@smu.edu
authors.forename: Dunming
authors.initials: D
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Stephanie
authors.initials: S
authors.lastname: Majkowicz
authors.forename: Thoris Hsin-Yuan
authors.initials: TH
authors.lastname: Pan
authors.forename: Katherine
authors.initials: K
authors.lastname: Kantardjieff
authors.forename: Ling
authors.initials: L
authors.lastname: Hua
mesh_terms: D000098:Acetophenones / Q000737:chemistry*; D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000235:genetics; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D001487:Basidiomycota / Q000201:enzymology*; D001665:Binding Sites; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D017354:Point Mutation; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D000098:Acetophenones; D007659:Ketones; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase