Molecular dynamics simulation to rationalize regioselective hydroxylation of aromatic substrates by soluble methane monooxygenase

SIGDEL, Sujan, HUI, Gao, SMITH, Thomas J., MURRELL, J. Colin and LEE, Jung-Kul (2015). Molecular dynamics simulation to rationalize regioselective hydroxylation of aromatic substrates by soluble methane monooxygenase. Bioorganic & Medicinal Chemistry Letters, 25 (7), 1611-1615.

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Official URL: http://dx.doi.org/10.1016/j.bmcl.2015.01.069
Link to published version:: 10.1016/j.bmcl.2015.01.069

Abstract

Soluble methane monooxygenase (sMMO) is a bacterial multicomponent enzyme that oxidizes a diverse range of substrates, including aromatic hydrocarbons. We have investigated enzyme–substrate interactions that govern oxidation regioselectivity at various sites of aromatic compounds using substrate docking and molecular dynamics (MD) simulations. Here, we studied the hydroxylation of toluene and ethyl benzene by two forms of Methylosinus trichosporium OB3b (sMMO), that is, wild-type (WT) and two active site mutants (L110Y/G). The two substrates, toluene and ethyl benzene, were docked into the active site of the WT and the L110Y/G mutant models of M. trichosporium OB3b sMMO using the available X-ray structure (PDB id 1MHZ). The trends observed in the formation of the experimental product were highly correlated with the results obtained from the relatively short MD simulation. These results show that our approach could be an attractive computational tool to rationalize the prediction of product ratios and specificities.

Item Type: Article
Additional Information: Available online 12 February 2015
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Identification Number: 10.1016/j.bmcl.2015.01.069
Depositing User: Jill Hazard
Date Deposited: 27 Apr 2015 11:16
Last Modified: 27 Apr 2015 11:16
URI: http://shura.shu.ac.uk/id/eprint/9677

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