Laccase redox potentials: pH dependence and mutants, a QM/MM study
Abstract
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.
Citation
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 . https://doi.org/10.1021/acs.jpcb.6b04978
Publication
Journal of Physical Chemistry B
Status
Peer reviewed
ISSN
1520-6106Type
Journal article
Description
The authors are grateful for funding by the Engineering and Physical Sciences Research Council, grant “Clean catalysis for sustainable development” (Ref. EP/J018139/1).Collections
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