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Inhibition of skeletal muscle S1-myosin ATPase by peroxynitrite

dc.contributor.authorTiago, Teresa
dc.contributor.authorS, Simão
dc.contributor.authorAureliano, M.
dc.contributor.authorMartín-Romero, Francisco Javier
dc.contributor.authorGutiérrez-Merino, Carlos
dc.date.accessioned2012-06-28T08:06:15Z
dc.date.available2012-06-28T08:06:15Z
dc.date.issued2006
dc.description.abstractExposure of myosin subfragment 1 (S1) to 3-morpholinosydnonimine (SIN-1) produced a time-dependent inhibition of the F-actin-stimulated S1 Mg2+-ATPase activity, reaching 50% inhibition with 46.7 ( 8.3 íM SIN-1 for 8.7 íM S1, that is, at a SIN-1/S1 molar ratio of approximately 5.5. The inhibition was due to the peroxynitrite produced by SIN-1 decomposition because (1) decomposed SIN-1 was found to have no effect on S1 ATPase activity, (2) addition of SIN-1 in the presence of superoxide dismutase and catalase fully prevented inhibition by SIN-1, and (3) micromolar pulses of chemically synthesized peroxynitrite produced inhibition of F-actin-stimulated S1 Mg2+-ATPase activity. In parallel, SIN-1 produced the inhibition of the nonphysiological Ca2+-dependent and K+/EDTA-dependent S1 ATPase activity of S1 and, therefore, suggested that the inhibition of F-actin-stimulated S1 Mg2+-ATPase activity is produced by the oxidation of highly reactive cysteines of S1 (Cys707 and Cys697), located close to the catalytic center. This point was further confirmed by the titration of S1 cysteines with 5,5¢-dithiobis(2- nitrobenzoic acid) and by the parallel decrease of Cys707 labeling by 5-(iodoacetamido)fluorescein, and it was reinforced by the fact that other common protein modifications produced by peroxynitrite, for example, protein carbonyl and nitrotyrosine formation, were barely detected at the concentrations of SIN-1 that produced more than 50% inhibition of the F-actin-stimulated S1 Mg2+-ATPase activity. Differential scanning calorimetry of S1 (untreated and treated with different SIN-1 concentrations) pointed out that SIN-1, at concentrations that generate micromolar peroxynitrite fluxes, impaired the ability of ADPâV1 to induce the intermediate catalytic transition state and also produced the partial unfolding of S1 that leads to an enhanced susceptibility of S1 to trypsin digestion, which can be fully protected by 2 mM GSH.por
dc.identifier.doi10.1021/bi0518500
dc.identifier.issn0006-2960
dc.identifier.urihttp://hdl.handle.net/10400.1/1355
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherAmerican Chemical Societypor
dc.relationCadmium and vanadium compounds interactions with sarcoplasmic reticulum calcium pump
dc.subjectMyosinpor
dc.subjectPeroxinitritepor
dc.titleInhibition of skeletal muscle S1-myosin ATPase by peroxynitritepor
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCadmium and vanadium compounds interactions with sarcoplasmic reticulum calcium pump
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCTI%2FQUI%2F38191%2F2001/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F20777%2F2004/PT
oaire.citation.endPage3804por
oaire.citation.issue45por
oaire.citation.startPage3794por
oaire.citation.titleBiochemistrypor
oaire.fundingStreamPOCI
oaire.fundingStreamSFRH
person.familyNameSimao
person.familyNameAureliano
person.familyNameGutierrez-Merino
person.givenNameSonia
person.givenNameManuel
person.givenNameCarlos
person.identifier584146
person.identifier.ciencia-idAA14-3490-DC5E
person.identifier.orcid0000-0002-0245-0633
person.identifier.orcid0000-0003-4858-3201
person.identifier.orcid0000-0003-3673-7007
person.identifier.ridI-3283-2012
person.identifier.ridK-4574-2014
person.identifier.scopus-author-id24067982400
person.identifier.scopus-author-id6603412860
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspor
rcaap.typearticlepor
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relation.isAuthorOfPublication.latestForDiscoverye4df724e-8bad-4f99-8e8b-f888b3c93692
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