Direct Evidence for a Peroxide Intermediate and a Reactive Enzyme-Substrate-Dioxygen Configuration in a Cofactor-free Oxidase - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Angewandte Chemie International Edition Année : 2014

Direct Evidence for a Peroxide Intermediate and a Reactive Enzyme-Substrate-Dioxygen Configuration in a Cofactor-free Oxidase

Résumé

Cofactor-free oxidases and oxygenases promote and control the reactivity of O-2 with limited chemical tools at their disposal. Their mechanism of action is not completely understood and structural information is not available for any of the reaction intermediates. Near-atomic resolution crystallography supported by incrystallo Raman spectroscopy and QM/MM calculations showed unambiguously that the archetypical cofactor-free uricase catalyzes uric acid degradation via a C5(S)-(hydro)peroxide intermediate. Low X-ray doses break specifically the intermediate C5OO(H) bond at 100K, thus releasing O-2 insitu, which is trapped above the substrate radical. The dose-dependent rate of bond rupture followed by combined crystallographic and Raman analysis indicates that ionizing radiation kick-starts both peroxide decomposition and its regeneration. Peroxidation can be explained by a mechanism in which the substrate radical recombines with superoxide transiently produced in the active site

Domaines

Chimie
Fichier principal
Vignette du fichier
Angewandte_Chemie_Vol_53_pp_13710.pdf (1.97 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Loading...

Dates et versions

hal-01572959 , version 1 (08-08-2017)

Identifiants

Citer

Soi Bui, David von Stetten, Pablo G. Jambrina, Thierry Prange, Nathalie Colloc'H, et al.. Direct Evidence for a Peroxide Intermediate and a Reactive Enzyme-Substrate-Dioxygen Configuration in a Cofactor-free Oxidase. Angewandte Chemie International Edition, 2014, 53 (50), pp.13710-13714. ⟨10.1002/anie.201405485⟩. ⟨hal-01572959⟩
266 Consultations
90 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More