Mechanism of glycoside hydrolysis: a comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanases
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Other documents of the author: Soliman, Mahmoud E. S.; Ruiz-Pernía, José Javier; Greig, Ian R.; Williams, Ian H.
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Title
Mechanism of glycoside hydrolysis: a comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanasesDate
2009Publisher
Royal Society of ChemistryISSN
1477-0520Bibliographic citation
SOLIMAN, Mahmoud ES, et al. Mechanism of glycoside hydrolysis: A comparative QM/MM molecular dynamics analysis for wild type and Y69F mutant retaining xylanases. Organic & Biomolecular Chemistry, 2009, vol. 7, no 24, p. 5236-5244.Type
info:eu-repo/semantics/articlePublisher version
https://pubs.rsc.org/en/content/articlehtml/2009/ob/b911644cVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
Computational simulations have been performed using hybrid quantum-mechanical/
molecular-mechanical potentials to investigate the catalytic mechanism of the retaining endo-b-1,
4-xylanase (BCX) from B. circulans. ... [+]
Computational simulations have been performed using hybrid quantum-mechanical/
molecular-mechanical potentials to investigate the catalytic mechanism of the retaining endo-b-1,
4-xylanase (BCX) from B. circulans. Two-dimensional potential-of-mean-force calculations based upon
molecular dynamics with the AM1/OPLS method for wild-type BCX with a p-nitrophenyl xylobioside
substrate in water clearly indicates a stepwise mechanism for glycosylation: the rate-determining step is
nucleophilic substitution by Glu78 to form the covalently bonded enzyme-substrate intermediate
without protonation of the leaving group by Glu172. The geometrical configuration of the transition
state for the enzymic reaction is essentially the same as found for a gas-phase model involving only the
substrate and a propionate/propionic acid pair to represent the catalytic glutamate/glutamic acid
groups. In addition to stabilizing the 2,5B boat conformation of the proximal xylose in the non-covalent
reactant complex of the substrate with BCX, Tyr69 lowers the free-energy barrier for glycosylation by
42 kJ mol-1 relative to that calculated for the Y69F mutant, which lacks the oxygen atom OY.
B3LYP/6-31+G* energy corrections reduce the absolute height of the barrier to reaction. In the
oxacarbenium ion-like transition state OY approaches closer to the endocyclic oxygen Oring of the sugar
ring but donates its hydrogen bond not to Oring but rather to the nucleophilic oxygen of Glu78.
Comparison of the average atomic charge distributions for the wild-type and mutant indicates that
charge separation along the bond between the anomeric carbon and Oring is matched in the former by a
complementary separation of charge along the OY–HY bond, corresponding to a pair of roughly
antiparallel bond dipoles, which is not present in the latter [-]
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