Molecular dynamics simulation to rationalize regioselective hydroxylation of aromatic substrates by soluble methane monooxygenase.
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.
Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
Sujan
S
Sigdel
Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul 143-701, Republic of Korea.
Gao
G
Hui
Biomedical Research Centre, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK.
Thomas J
TJ
Smith
School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
J Colin
JC
Murrell
Department of Chemical Engineering, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul 143-701, Republic of Korea. Electronic address: jkrhee@konkuk.ac.kr.
Jung-Kul
JK
Lee
D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D020602:Methylosinus trichosporium / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010105:Oxygenases / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D013237:Stereoisomerism
D006841:Hydrocarbons, Aromatic; D010105:Oxygenases; C021555:methane monooxygenase
MD simulation; Oxidation; Regioselectivity; Soluble methane monooxygenase; Substrate docking