1ZMT

Structure of haloalcohol dehalogenase HheC of Agrobacterium radiobacter AD1 in complex with (R)-para-nitro styrene oxide, with a water molecule in the halide-binding site

Summary for 1ZMT

• Entry DOI: 10.2210/pdb1zmt/pdb
• Related: 1ZMO 1ZO8
• Descriptor: Haloalcohol dehalogenase HheC, (R)-PARA-NITROSTYRENE OXIDE (3 entities in total)
• Functional Keywords: haloalcohol dehalogenase, halohydrin dehalogenase, epoxide catalysis, enantioselectivity, lyase
• Biological source: Agrobacterium tumefaciens
• Total number of polymer chains: 4
• Total formula weight: 112579.25

Authors

de Jong, R.M.,Tiesinga, J.J.W.,Villa, A.,Tang, L.,Janssen, D.B.,Dijkstra, B.W. (deposition date: 2005-05-10, release date: 2005-10-04, Last modification date: 2024-02-14)

Primary citation

de Jong, R.M.,Tiesinga, J.J.W.,Villa, A.,Tang, L.,Janssen, D.B.,Dijkstra, B.W.
Structural Basis for the Enantioselectivity of an Epoxide Ring Opening Reaction Catalyzed by Halo Alcohol Dehalogenase HheC.
J.Am.Chem.Soc., 127:13338-13343, 2005

PubMed 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.

PubMed: 16173767
DOI: 10.1021/ja0531733

Experimental method

X-RAY DIFFRACTION (1.7 Å)