title: Insights into structure and redox potential of lignin peroxidase from QM/MM calculations.
abstract: Redox potentials are computed for the active form (compound I) of lignin peroxidase (LiP) using a suitable QM/MM methodology (B3LYP/SDD/6-311G**//BP86/SVP:CHARMM). Allowing for dynamic conformational averaging, a potential of 0.67(33) V relative to ferrocenium/ferrocene is obtained for the active form with its oxoiron(iv) core. The computed redox potential is very sensitive to the charge distribution around the active site: protonation of titratable residues close to the metal center increases the redox potential, thereby rationalising the known pH dependence of LiP activity. A simple MM-charge deletion scheme is used to identify residues that are critical for the redox potential. Two mutant proteins are studied through homology modelling, E40Q and D183N, which are predicted to have an increased redox potential by 140 mV and 190 mV, respectively, relative to the wild type. These mutant proteins are thus promising targets for synthesis and further exploration toward a rational design of biocatalytic systems for oxidative degradation of lignin.
authors.affiliation: EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. mb105@st-andrews.ac.uk.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Castro
authors.affiliation: EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. mb105@st-andrews.ac.uk.
authors.forename: L Ellis
authors.initials: LE
authors.lastname: Crawford
authors.affiliation: EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. mb105@st-andrews.ac.uk.
authors.forename: Archford
authors.initials: A
authors.lastname: Mutengwa
authors.affiliation: EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. mb105@st-andrews.ac.uk.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Götze
authors.affiliation: EastChem School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK. mb105@st-andrews.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Bühl
mesh_terms: D005296:Ferrous Compounds / Q000737:chemistry / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D000075163:Metallocenes; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory
chemical_list: D005296:Ferrous Compounds; D000075163:Metallocenes; C064804:ferrocenium; D010544:Peroxidases; C042858:lignin peroxidase; C004998:ferrocene