title: X-ray, ESR, and quantum mechanics studies unravel a spin well in the cofactor-less urate oxidase.
abstract: Urate oxidase (EC 1.7.3.3 or UOX) catalyzes the conversion of uric acid using gaseous molecular oxygen to 5-hydroxyisourate and hydrogen peroxide in absence of any cofactor or transition metal. The catalytic mechanism was investigated using X-ray diffraction, electron spin resonance spectroscopy (ESR), and quantum mechanics calculations. The X-ray structure of the anaerobic enzyme-substrate complex gives credit to substrate activation before the dioxygen fixation in the peroxo hole, where incoming and outgoing reagents (dioxygen, water, and hydrogen peroxide molecules) are handled. ESR spectroscopy establishes the initial monoelectron activation of the substrate without the participation of dioxygen. In addition, both X-ray structure and quantum mechanic calculations promote a conserved base oxidative system as the main structural features in UOX that protonates/deprotonates and activate the substrate into the doublet state now able to satisfy the Wigner's spin selection rule for reaction with molecular oxygen in its triplet ground state.
authors.affiliation: LCRB, UMR 8015 CNRS, Faculté de Pharmacie, Université Paris Descartes, 75270 Paris Cedex 06, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Gabison
authors.forename: Claude
authors.initials: C
authors.lastname: Chopard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Colloc'h
authors.forename: Fabienne
authors.initials: F
authors.lastname: Peyrot
authors.forename: Bertrand
authors.initials: B
authors.lastname: Castro
authors.forename: Mohamed
authors.initials: M
authors.lastname: El Hajji
authors.forename: Muhannad
authors.initials: M
authors.lastname: Altarsha
authors.forename: Gerald
authors.initials: G
authors.lastname: Monard
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chiadmi
authors.forename: Thierry
authors.initials: T
authors.lastname: Prangé
mesh_terms: D001231:Aspergillus flavus / Q000737:chemistry / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004578:Electron Spin Resonance Spectroscopy; D008958:Models, Molecular; D011485:Protein Binding; D011789:Quantum Theory; D014503:Urate Oxidase / Q000737:chemistry* / Q000378:metabolism*; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D014527:Uric Acid; D014503:Urate Oxidase