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Quantum mechanical study of the hydride shift step in the xylose isomerase catalytic reaction with the fragment self‐consistent field method
Author(s) -
Ferenczy György G.,
Náray–Szabó Gábor,
Várnai Péter
Publication year - 1999
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/(sici)1097-461x(1999)75:3<215::aid-qua11>3.0.co;2-i
Subject(s) - chemistry , hydride , computational chemistry , polarizability , delocalized electron , molecular orbital , chemical physics , molecule , metal , organic chemistry
The rate‐limiting hydride shift step of the xylose isomerase catalytic reaction was studied with our fragment self‐consistent field method designed for very large electronic systems. The method is based on a model partitioning the enzyme and the surrounding biophase into central, polarizable and nonpolarizable regions, respectively. The central region, including the substrate and its close environment, is embedded in a polarizable environment composed of the neighboring amino‐acid residues. The union of these two regions is then surrounded by atomic point charges representing the nonpolarizable region including distant residues, a few bulk and all structural water molecules. The central region is treated in a self‐consistent manner at the semiempirical NDDO PM3 level using the conventional molecular orbital approach. Boundary atoms, connecting the central region with its environment, are represented by hybrid orbitals directed either toward its interior or along further bonds connecting these atoms to the polarizable region. This latter is treated in terms of one‐ and two‐center strictly localized molecular orbitals, representing lone pairs and diatomic bonds, respectively. Their polarities are determined via a coupled secular equation not allowing delocalization among bonds, thus being mathematically considerably simpler. Activation energies of the hydride shift reaction were calculated for three metal cations, Mg 2+ , Al 3+ , and Zn 2+ . The lowest activation energy was found for the activating Mg 2+ cation. An analysis of the initial and transition‐state structures show that electrostatic effects are especially important in determining the reaction barrier. Results are confronted with our former hypothesis stating that it is charge transfer to the catalytic metal that determines whether a cation will activate or inactivate the catalytic reaction. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 75: 215–222, 1999