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dc.contributor.authorAlves, Rui
dc.contributor.authorHerrero Perpiñán, Enrique
dc.contributor.authorSorribas Tello, Albert
dc.date.accessioned2015-07-17T11:49:20Z
dc.date.issued2004
dc.identifier.issn1097-0134
dc.identifier.urihttp://hdl.handle.net/10459.1/48616
dc.description.abstractGrx5 is a Saccharomyces cerevi- siae glutaredoxin involved in iron-sulfur cluster (FeSC) biogenesis. Previous work suggests that Grx5 is involved in regulating protein cysteine glutathio- nylation, prompting several questions about the systemic role of Grx5. First, is the regulation of mixed protein-glutathione disulfide bridges in FeSC biosynthetic proteins by Grx5 sufficient to account for the observed phenotypes of the ⌬grx5 mutants? If so, does Grx5 regulate the oxidation state of mixed protein-glutathione disulfide bridges in FeSC bio- genesis in general? Alternatively, can the ⌬grx5 mutant phenotypes be explained if Grx5 acts on just one or a few of the FeSC biogenesis proteins? In the first part of this article, we address these questions by building and analyzing a mathematical model of FeSC biosynthesis. We show that, indepen- dent of the tested parameter values, the dynamic behavior observed in cells depleted of Grx5 can only be qualitatively reproduced if Grx5 acts by regulat- ing the initial assembly of FeSC in scaffold proteins. This can be achieved by acting on the cysteine desulfurase (Nfs1) activity and/or on scaffold func- tionality. In the second part of this article, we use structural bioinformatics methods to evaluate the possibility of interaction between Grx5 and proteins involved in FeSC biogenesis. Based on such methods, our results indicate that the proteins with which Grx5 is more likely to interact are consistent with the ki- netic modeling results. Thus, our theoretical studies, combined with known Grx5 biochemistry, suggest that Grx5 acts on FeSC biosynthesis by regulating the redox state of important cysteine residues in Nfs1 and/or in the scaffold proteins where FeSC initially assemble.ca_ES
dc.language.isoengca_ES
dc.publisherJohn Wiley & Sonsca_ES
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1002/prot.20228ca_ES
dc.relation.ispartofProteins: Structure, Function, and Bioinformatics, 2004, vol 57, p. 481-492ca_ES
dc.rights(c) WILEY-LISS, 2004ca_ES
dc.subjectKinetic modelingca_ES
dc.subjectMetabolic reconstructionca_ES
dc.subjectSystemic biologyca_ES
dc.subjectStructural modelingca_ES
dc.titlePredictive Reconstruction of the Mitochondrial Iron-Sulfur Cluster Assembly Metabolism. II. Role of Glutaredoxin Grx5ca_ES
dc.typearticleca_ES
dc.identifier.idgrec002789
dc.type.versionpublishedVersionca_ES
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccessca_ES
dc.identifier.doihttps://doi.org/10.1002/prot.20228
dc.date.embargoEndDate2025-01-01


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