ISSN:
1573-4951
Keywords:
enzyme mechanism
;
flavoenzyme
;
force field
;
ligand docking
;
QM/MM
;
semiempirical calculation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The complex structure of glucose oxidase (GOX) with the substrate glucose was determined using a docking algorithm and subsequent molecular dynamics simulations. Semiempirical quantum chemical calculations were used to investigate the role of the enzyme and FAD co-enzyme in the catalytic oxidation of glucose. On the basis of a small active site model, substrate binding residues were determined and heats of formation were computed for the enzyme substrate complex and different potential products of the reductive half reaction. The influence of the protein environment on the active site model was estimated with a point charge model using a mixed QM/MM method. Solvent effects were estimated with a continuum model. Possible modes of action are presented in relation to experimental data and discussed with respect to related enzymes. The calculations indicate that the redox reaction of GOX differs from the corresponding reaction of free flavins as a consequence of the protein environment. One of the active site histidines is involved in substrate binding and stabilization of potential intermediates, whereas the second histidine is a proton acceptor. The former one, being conserved in a series of oxidoreductases, is also involved in the stabilization of a C4a-hydroperoxy dihydroflavin in the course of the oxidative half reaction.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008020124326
Permalink