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

GOMEZ, MA C.; NEUMAN, NICOLAS; DALOSTO, S.D; GOZALEZ, PABLO; RIZZI, ALBERTO; BRONDINO, CARLOS; JOSE MOURA

JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2015 vol. 20 p. 233 - 242

0949-8257

p { margin-bottom: 0.08in; } Aldehyde oxidoreductase from Desulfovibrio gigas (DgAOR) is a homodimeric molybdenum-containing protein that catalyzes the oxidative hydroxylation of aldehydes to carboxylic acids and contains two major domains called Mo and FeS domains, the latter containing two [2Fe-2S] centers called FeS 1 and FeS 2. The electron transfer reaction inside DgAOR is proposed to be performed through a chemical pathway linking Mo and the two FeS clusters. The proposed electron transfer pathway between Mo and FeS 1 is formed by the Mo pyranopterin ligand and the gamma sulfur atom from Cys 139 coordinated to the nearest iron atom of FeS 1. EPR studies performed on reduced as-prepared DgAOR showed that this pathway is able to transmit very weak exchange interactions between Mo(V) and reduced FeS 1. Similar EPR studies but performed on DgAOR samples inhibited with glycerol and ethylene glycol showed that the value of the exchange coupling constant J increases ~2 times upon alcohol inhibition. Structural studies in these DgAOR samples have demonstrated that the Mo-FeS 1 bridging pathway does not show significant differences, confirming that the changes in J observed upon inhibition cannot be ascribed to structural changes associated neither with pyranopterin and FeS 1 nor with changes in the electronic structure of FeS 1, as its EPR properties remain unchanged. Theoretical calculations indicate that the changes in J detected by EPR are related to changes in the electronic structure of Mo(V) determined by the replacement of the OHx labile ligand for an alcohol molecule. Since the relationship between electron transfer rate and isotropic exchange interaction, the present results suggest that the intraenzyme electron transfer process mediated by the pyranopterin moiety is governed by a Mo ligand-based regulatory mechanism.>I am pleased to inform you that your revised >manuscript, "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" (JBIC-14-07-00105.R1) has been >accepted for publication. Thus I am forwarding >your materials to the publisher. Please note >that if you have not yet uploaded a main text >.rtf or .doc file into the Manuscript Central >web-based system, you will need provide such a >file immediately. Supplementary Material files, >on the other hand, must be in .pdf format. >Please attach any such necessary files to an email addressed to >jbic@umn.edu >in order for the publisher to process your >manuscript. If you have any questions about the >size of your file or how best to attach it, >contact our editorial assistant at this address right away. > >I appreciate your support of JBIC. > >Sincerely, > >Dr. Paul Bernhardt