Structural Basis for the Enantioselectivity of an Epoxide Ring Opening Reaction Catalyzed by Halo Alcohol Dehalogenase HheC
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- 作者：René ; M. de Jong ; Jan J. W. Tiesinga ; Alessandra Villa ; Lixia Tang ; Dick B. Janssen ; and Bauke W. Dijkstra
- 刊名：Journal of the American Chemical Society
- 出版年：2005
- 出版时间：September 28, 2005
- 年：2005
- 卷：127
- 期：38
- 页码：13338 - 13343
- 全文大小：464K
- 年卷期：v.127,no.38(September 28, 2005)
- ISSN：1520-5126
文摘
Halo alcohol dehalogenase HheC catalyzes the highly enantioselective dehalogenation of vicinalhalo alcohols to epoxides, as well as the reverse reaction, the enantioselective and 
-regioselectivenucleophilic ring opening of epoxides by pseudo-halides such as azide and cyanide. To investigate thislatter reaction, we determined X-ray structures of complexes of HheC with the favored and unfavoredenantiomers of para-nitrostyrene oxide. The aromatic parts of the two enantiomers bind in a very similarway, but the epoxide ring of the unfavored (S)-enantiomer binds in a nonproductive inverted manner, withthe epoxide oxygen and C 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 asingle hydrogen bond in the S bound state with respect to the R bound state. Our results indicate that it isthe nonproductive binding of the unfavored (S)-enantiomer, rather than the difference in affinity for the twoenantiomers, that allows HheC to catalyze the azide-mediated ring opening of para-nitrostyrene oxide withhigh enantioselectivity. This work represents a rare opportunity to explain the enantioselectivity of anenzymatic reaction by comparison of crystallographic data on the binding of both the favored and unfavoredenantiomers.
-regioselectivenucleophilic ring opening of epoxides by pseudo-halides such as azide and cyanide. To investigate thislatter reaction, we determined X-ray structures of complexes of HheC with the favored and unfavoredenantiomers of para-nitrostyrene oxide. The aromatic parts of the two enantiomers bind in a very similarway, but the epoxide ring of the unfavored (S)-enantiomer binds in a nonproductive inverted manner, withthe epoxide oxygen and C 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 asingle hydrogen bond in the S bound state with respect to the R bound state. Our results indicate that it isthe nonproductive binding of the unfavored (S)-enantiomer, rather than the difference in affinity for the twoenantiomers, that allows HheC to catalyze the azide-mediated ring opening of para-nitrostyrene oxide withhigh enantioselectivity. This work represents a rare opportunity to explain the enantioselectivity of anenzymatic reaction by comparison of crystallographic data on the binding of both the favored and unfavoredenantiomers.