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

Bioorganic & Medicinal Chemistry Letters
Sujan SigdelJung-Kul Lee

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 1 MHZ). 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.

References

Oct 11, 2003·FEMS Microbiology Reviews·Joseph G LeahySuzanne M Morcomb
Jul 5, 2006·Environmental Microbiology·Nicholas V ColemanAndrew J Holmes
Sep 29, 2006·Journal of Medicinal Chemistry·Julian Tirado-Rives, William L Jorgensen
Dec 20, 2013·International Journal of Molecular Sciences·Lovorka Perić-HasslerDaan P Geerke
Jun 14, 2014·The FEBS Journal·Ponnandy PrabhuJung-Kul Lee

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Citations

May 4, 2017·Scientific Reports·Elisa LanfranchiAnton Glieder

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