Laccase redox potentials: pH dependence and mutants, a QM/MM study
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We have studied the T. versicolor laccase T1 site redox potential (RP) at the M06/6-311++G**/SDD(Cu) level of theory, employing QM/MM optimised geometries (RI-BP86/def2-SVP/def2-TZVP(Cu):CHARMM) of the whole protein system with electronic embedding. The oxidation state of the trinuclear cluster was found to affect the T1 site RP by about 0.2-0.3 V, depending on the protein protonation state. The computed laccase RP can be drastically lowered upon introduction of a protonation state corresponding to a neutral environment, by up to -1.37 V, which is likely an overestimation of the effect in vivo. The gradual change of the protonation state by single points without optimisation or equilibration results in a change that is even larger, namely up to about -2.6 V. Thus, the preferred protein conformation supports a high redox potential, compensating for the RP-lowering effect of surface charges. The predicted change in RP on going to the F463M mutant, ca. -0.1 V, is consistent with observations for a related laccase. Based on our results, we also propose and test a D206N mutant, but find it to be locked in a conformation with slightly lower RP.
Goetze , J P & Buehl , M 2016 , ' Laccase redox potentials: pH dependence and mutants, a QM/MM study ' Journal of Physical Chemistry B , vol 120 , no. 35 , pp. 9265-9276 . DOI: 10.1021/acs.jpcb.6b04978
Journal of Physical Chemistry B
Copyright © 2016 American Chemical Society. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://dx.doi.org/10.1021/acs.jpcb.6b04978
The authors are grateful for funding by the Engineering and Physical Sciences Research Council, grant “Clean catalysis for sustainable development” (Ref. EP/J018139/1).
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