Intermediates in Dioxygen Activation by Methane Monooxygenase: A QM/MM Study

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• 作者：David Rinaldo ; Dean M. Philipp ; Stephen J. Lippard ; Richard A. Friesner
• 刊名：Journal of the American Chemical Society
• 出版年：2007
• 出版时间：March 21, 2007
• 年：2007
• 卷：129
• 期：11
• 页码：3135 - 3147
• 全文大小：433K
• 年卷期：v.129,no.11(March 21, 2007)
• ISSN：1520-5126

文摘

Protein effects in the activation of dioxygen by methane monooxygenase (MMO) were investigatedby using combined QM/MM and broken-symmetry Density Functional Theory (DFT) methods. The effectsof a novel empirical scheme recently developed by our group on the relative DFT energies of the variousintermediates in the catalytic cycle are investigated. Inclusion of the protein leads to much better agreementbetween the experimental and computed geometric structures for the reduced form (MMOH_red). Analysisof the electronic structure of MMOH_red reveals that the two iron atoms have distinct environments. Differentcoordination geometries tested for the MMOH_peroxo intermediate reveal that, in the protein environment,the mages/entities/mgr.gif">-mages/gifchars/eta.gif" BORDER=0 >²,mages/gifchars/eta.gif" BORDER=0 >² structure is more stable than the others. Our analysis also shows that the protein helps to drivereactants toward products along the reaction path. Furthermore, these results demonstrate the importanceof including the protein environment in our models and the usefulness of the QM/MM approach for accuratemodeling of enzymatic reactions. A discrepancy remains in our calculation of the Fe-Fe distance in ourmodel of H_Q as compared to EXAFS data obtained several years ago, for which we currently do not havean explanation.