title: DFT study of the active site of the XoxF-type natural, cerium-dependent methanol dehydrogenase enzyme.
abstract: Rare-earth metal cations have recently been demonstrated to be essential co-factors for the growth of the methanotrophic bacterium Methylacidiphilum fumariolicum SolV. A crystal structure of the rare-earth-dependent methanol dehydrogenase (MDH) includes a cerium cation in the active site. Herein, the Ce-MDH active site has been analyzed through DFT calculations. The results show the stability of the Ce(III)-pyrroloquinoline quinone (PQQ) semiquinone configuration. Calculations on the active oxidized form of this complex indicate a 0.81 eV stabilization of the PQQ(0) LUMO at cerium versus calcium, supporting the observation that the cerium cation in the active site confers a competitive advantage to Methylacidiphilum fumariolicum SolV. Using reported aqueous electrochemical data, a semi-empirical correlation was established based on cerium(IV/III) redox potentials. The correlation allowed estimation of the cerium oxidation potential of +1.35 V versus saturated calomel electrode (SCE) in the active site. The results are expected to guide the design of functional model complexes and alcohol-oxidation catalysts based on lanthanide complexes of biologically relevant quinones.
authors.affiliation: Department of Chemistry, University of Pennsylvania, P. Roy and Diana T. Vagelos Laboratories, Philadlephia, PA 19104 (USA).
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bogart
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lewis
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Schelter
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D002563:Cerium / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010084:Oxidation-Reduction; D045542:PQQ Cofactor / Q000737:chemistry* / Q000378:metabolism; D061327:Verrucomicrobia / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism
chemical_list: D002563:Cerium; D045542:PQQ Cofactor; C037275:2,7,9-tricarboxypyrrolo(2,3-f)quinoline-4-ol-5-one; D000429:Alcohol Oxidoreductases; C019641:alcohol dehydrogenase (acceptor)
keywords: cerium; density functional calculations; metalloenzymes; quinones; redox chemistry