Combined X-Ray Diffraction and QM/MM Study of the Burkholderia cepacia Lipase-Catalyzed Secondary Alcohol Esterification
| Autor: | Marija Luić, Igor Ceilinger, Zoran Štefanić, Tihana Lenac, Dusanka Janezic, Milan Hodoscek, Sanja Tomić, Ivana Leščić Ašler, Dragan Šepac |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Stereochemistry Burkholderia cepacia lipase Molecular modeling crystallography Burkholderia cepacia Crystallography X-Ray Catalysis Phosphates QM/MM chemistry.chemical_compound X-Ray Diffraction Biomimetic Materials Materials Chemistry Physical and Theoretical Chemistry Lipase Binding Sites Esterification Molecular Structure biology Hydrogen bond Active site Substrate (chemistry) Hydrogen Bonding Phosphonate Protein Structure Tertiary Surfaces Coatings and Films chemistry Covalent bond Alcohols biology.protein Enantiomer |
| DOI: | 10.1021/jp077717u |
| Popis: | To understand the origin of high enantioselectivity of Burkholderia cepacia lipase (BCL) towards secondary alcohol, (R, S)-1-phenoxy-2-hydroxybutane (1) and its ester (E1) we determined the crystal structure of BCL complexed with phosphonate analogue of S-E1 and accomplished a series of MM, MC and QM/MM studies. We have found that the inhibitor in the S configuration binds into the BCL active site in the same manner as the R isomer, with an important difference: while in case of the R-inhibitor the H-bond between its alcohol oxygen and catalytic His286 can be formed, in the case of the S-inhibitor this is not possible. Molecular modeling for both E1 enantiomers revealed orientations in which all hydrogen bonds characteristic of productive binding are formed. In order to check possibility of chemical transformation, four different orientations of the substrate (two for each enantiomer) were chosen and a series of ab initio QM/MM calculations were accomplished. Starting from the covalent complex we modeled the ester (E1) hydrolysis and the alcohol (1) esterification. The calculations revealed that ester release is possible starting with all four covalent complexes. Alcohol release from the BCL− E1 complex in which the S-substrate is bound in the same manner as the S-inhibitor in the crystal structure however is not possible. These results show that the crystallographically determined binding modes should be taken with caution when modeling chemical reactions. |
| Databáze: | OpenAIRE |
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