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Structural basis for the enantioselectivity of an epoxide ring opening reaction catalyzed by halo alcohol dehalogenase HheC
- Source :
- Journal of the American Chemical Society, 127(38), 13338-13343. AMER CHEMICAL SOC
- Publication Year :
- 2005
- Publisher :
- AMER CHEMICAL SOC, 2005.
-
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.
- Subjects :
- Models, Molecular
MECHANISM
Stereochemistry
Hydrolases
Protein Conformation
Halohydrin dehalogenase
Epoxide
010402 general chemistry
Ring (chemistry)
Crystallography, X-Ray
01 natural sciences
Biochemistry
Catalysis
Protein Structure, Secondary
chemistry.chemical_compound
Colloid and Surface Chemistry
Nucleophile
HALOHYDRIN DEHALOGENASE
PROGRAM
GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries)
Dehalogenase
010405 organic chemistry
Chemistry
CRYSTALLOGRAPHY
Enantioselective synthesis
Regioselectivity
SITE
Hydrogen Bonding
Stereoisomerism
General Chemistry
FREE-ENERGY
SIMULATIONS
0104 chemical sciences
MOLECULAR-DYNAMICS
Alcohols
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING
Epoxy Compounds
Azide
ENZYMES
AGROBACTERIUM-RADIOBACTER
Subjects
Details
- Language :
- English
- ISSN :
- 00027863
- Volume :
- 127
- Issue :
- 38
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....624b65ff05eaffc981d5d10febe613b2