Theoretical study of crystal structure of WrbA from E. coli in complex with benzoquinone using QM calculations of charge transfer rates

David Řeha1,2, Oksana Degtjarik2, Michal Kutý1,2, Ivana Kutá-Smatanová1,2, Rüdiger Ettrich1,2, Jannette Carey1,3

1Center for Nanobiology and Structural Biology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Zámek 136, 373 33 Nové Hrady, Czech Republic,
2Faculty of Science, University of South Bohemia, Branišovska 31, 370 05 České Budějovice, Czech Republic
3Chemistry Department, Princeton University, Princeton, New Jersey 08544-1009, USA

The computational methods are applied to compare the electron-transfer probability for two distinct crystal structures of the Escherichia coli protein WrbA, an FMN-dependent NAD(P)H:quinone oxidoreductase, with the bound substrate benzoquinone. The computational methods were based on the combination of quantum mechanics/molecular mechanics approach, semi-empirical methods and quantum mechanical (QM) calculations of charge transfer rates using Marcus equation. The calculations indicate that the position of benzoquinone in a new structure reported here and solved at 1.33 Å resolution is more likely to be relevant for the physiological reaction of WrbA than a previously reported crystal structure [1] in which benzoquinone is shifted by ~5 Å. Because the true electron-acceptor substrate for WrbA is not yet known, the present results can serve to constrain computational docking attempts with potential substrates that may aid in identifying the natural substrate(s) and physiological role(s) of this enzyme. The approach used here highlights a role for QM calculations in crystal structure interpretation.

1.         Andrade, S.L.; Patridge, E.V.; Ferry, J.G.; Einsle, O. J. Bacteriol. 2007, 189, 9101-9107

This work was supported by the Czech Science Foundation (project no GA15-12816S).