title: Structural basis for the enantioselectivity of an epoxide ring opening reaction catalyzed by halo alcohol dehalogenase HheC.
abstract: Halo alcohol dehalogenase HheC catalyzes the highly enantioselective dehalogenation of vicinal halo alcohols to epoxides, as well as the reverse reaction, the enantioselective and beta-regioselective nucleophilic ring opening of epoxides by pseudo-halides such as azide and cyanide. To investigate this latter reaction, we determined X-ray structures of complexes of HheC with the favored and unfavored enantiomers of para-nitrostyrene oxide. The aromatic parts of the two enantiomers bind in a very similar way, but the epoxide ring of the unfavored (S)-enantiomer binds in a nonproductive inverted manner, with the epoxide oxygen and Cbeta atom positions interchanged with respect to those of the favored (R)-enantiomer. The calculated difference in relative Gibbs binding energy is in agreement with the observed loss of a single hydrogen bond in the S bound state with respect to the R bound state. Our results indicate that it is the nonproductive binding of the unfavored (S)-enantiomer, rather than the difference in affinity for the two enantiomers, that allows HheC to catalyze the azide-mediated ring opening of para-nitrostyrene oxide with high enantioselectivity. This work represents a rare opportunity to explain the enantioselectivity of an enzymatic reaction by comparison of crystallographic data on the binding of both the favored and unfavored enantiomers.
authors.affiliation: Department of Biophysical Chemistry, University of Groningen, Nijenborgh 4, NL-9747 AG Groningen, The Netherlands.
authors.forename: René M
authors.initials: RM
authors.lastname: de Jong
authors.forename: Jan J W
authors.initials: JJ
authors.lastname: Tiesinga
authors.forename: Alessandra
authors.initials: A
authors.lastname: Villa
authors.forename: Lixia
authors.initials: L
authors.lastname: Tang
authors.forename: Dick B
authors.initials: DB
authors.lastname: Janssen
authors.forename: Bauke W
authors.initials: BW
authors.lastname: Dijkstra
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D006860:Hydrogen Bonding; D006867:Hydrolases / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D004852:Epoxy Compounds; D006867:Hydrolases; C113022:haloalcohol dehalogenase