title: Pyranopterin conformation defines the function of molybdenum and tungsten enzymes.
abstract: We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, AB, Canada T6G 2H7.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rothery
authors.forename: Benjamin
authors.initials: B
authors.lastname: Stein
authors.forename: Matthew
authors.initials: M
authors.lastname: Solomonson
authors.forename: Martin L
authors.initials: ML
authors.lastname: Kirk
authors.forename: Joel H
authors.initials: JH
authors.lastname: Weiner
mesh_terms: D003461:Crystallography; D004798:Enzymes / Q000737:chemistry*; D007506:Iron-Sulfur Proteins; D008958:Models, Molecular; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry*; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D017510:Protein Folding; D011622:Pterins / Q000737:chemistry*; D050876:Sulfite Oxidase; D014414:Tungsten / Q000737:chemistry*; D014968:Xanthine Dehydrogenase
chemical_list: D004798:Enzymes; D007506:Iron-Sulfur Proteins; D011622:Pterins; C490076:pyranopterin; D008982:Molybdenum; D010088:Oxidoreductases; D014968:Xanthine Dehydrogenase; D050876:Sulfite Oxidase; C045664:dimethyl sulfoxide reductase; D014414:Tungsten