Isotropic exchange interaction between Mo and the proximal FeS center in the xanthine oxidase family member aldehyde oxidoreductase from Desulfovibrio gigas on native and polyalcohol inhibited samples: an EPR and QM/MM study

MARÍA CECILIA GÓMEZ; NICOLÁS I. NEUMAN; SERGIO D. DALOSTO; PABLO J. GONZÁLEZ; JOSÉ J. G. MOURA; ALBERTO C. RIZZI; CARLOS D. BRONDINO

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2014 p. 233 - 242

0949-8257

Aldehyde oxidoreductase from Desulfovibriogigas (DgAOR) is a homodimeric molybdenum-containingprotein that catalyzes the hydroxylation of aldehydes tocarboxylic acids and contains a Mo-pyranopterin active siteand two FeS centers called FeS 1 and FeS 2. The electrontransfer reaction inside DgAOR is proposed to be performedthrough a chemical pathway linking Mo and thetwo FeS clusters involving the pyranopterin ligand. EPRstudies performed on reduced as-prepared DgAOR showedthat this pathway is able to transmit very weak exchangeinteractions between Mo(V) and reduced FeS 1. SimilarEPR studies but performed on DgAOR samples inhibitedwith glycerol and ethylene glycol showed that the value ofthe exchange coupling constant J increases *2 times uponalcohol inhibition. Structural studies in these DgAORsamples have demonstrated that the Mo?FeS 1 bridgingpathway does not show significant differences, confirmingthat the changes in J observed upon inhibition cannot beascribed to structural changes associated neither withpyranopterin and FeS 1 nor with changes in the electronicstructure of FeS 1, as its EPR properties remain unchanged.Theoretical calculations indicate that the changes inJ detected by EPR are related to changes in the electronicstructure of Mo(V) determined by the replacement of theOHx labile ligand for an alcohol molecule. Since therelationship between electron transfer rate and isotropicexchange interaction, the present results suggest that theintraenzyme electron transfer process mediated by thepyranopterin moiety is governed by a Mo ligand-basedregulatory mechanism.