Allosteric inhibition of a-thrombin enzymatic activity with ultrasmall gold nanoparticles

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dc.citation.volume1pt_BR
dc.contributor.authorLira, André [UNIFESP]
dc.contributor.authorFerreira, Rodrigo [UNIFESP]
dc.contributor.authorTorquato, Ricardo [UNIFESP]
dc.contributor.authorOliva, Maria L.V. [UNIFESP]
dc.contributor.authorSchuck, Peter
dc.contributor.authorSousa, Alioscka A [UNIFESP]
dc.contributor.authorLatteshttp://lattes.cnpq.br/2456185746978277pt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/2747045352050363pt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/3995278540776284pt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/5832778223847349pt_BR
dc.contributor.authorLatteshttp://lattes.cnpq.br/1447746283394507pt_BR
dc.contributor.institutionUniversidade Federal de São Paulo - UNIFESPpt_BR
dc.date.accessioned2021-06-11T10:32:19Z
dc.date.available2021-06-11T10:32:19Z
dc.date.issued2018-09-24
dc.description.abstractThe catalytic activity of enzymes can be regulated by interactions with synthetic nanoparticles (NPs) in a number of ways. To date, however, the potential use of NPs as allosteric effectors has not been investigated in detail. Importantly, targeting allosteric (distal) sites on the enzyme surface could afford unique ways to modulate the activity, allowing for either enzyme activation, partial or full inhibition. Using p-mercaptobenzoic acid-coated ultrasmall gold NPs (AuMBA) and human a-thrombin as a model system, here we experimentally tested the hypothesis that enzyme activity could be regulated through ultrasmall NP interactions at allosteric sites. We show that AuMBA interacted selectively and reversibly around two positively charged regions of the thrombin surface (exosites 1 and 2) and away from the active site. NP complexation at the exosites transmitted long-range structural changes over to the active site, altering both substrate binding affinity and catalysis. Significantly, thrombin activity was partially reduced – but not completely inhibited – by interactions with AuMBA. These findings indicate that interactions of proteins with ultrasmall NPs may mimic a typical biomolecular complexation event, and suggest the prospect of using ultrasmall particles as synthetic receptors to allosterically regulate protein functionen
dc.description.provenanceSubmitted by Alioscka Sousa (alioscka.sousa@unifesp.br) on 2021-06-10T22:24:30Z No. of bitstreams: 1 2019_NanoscaleAdvances.pdf: 2732044 bytes, checksum: 3a014abcbd15fadf2ad9055ca2c27893 (MD5)en
dc.description.provenanceApproved for entry into archive by Mariusa Loução (mariusa.loucao@unifesp.br) on 2021-06-11T10:32:19Z (GMT) No. of bitstreams: 1 2019_NanoscaleAdvances.pdf: 2732044 bytes, checksum: 3a014abcbd15fadf2ad9055ca2c27893 (MD5)en
dc.description.provenanceMade available in DSpace on 2021-06-11T10:32:19Z (GMT). No. of bitstreams: 1 2019_NanoscaleAdvances.pdf: 2732044 bytes, checksum: 3a014abcbd15fadf2ad9055ca2c27893 (MD5) Previous issue date: 2018-09-24en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipID2013/18481-5pt_BR
dc.format.extent378-388pt_BR
dc.identifierhttps://pubs.rsc.org/en/content/articlelanding/2019/na/c8na00081f#!divAbstractpt_BR
dc.identifier.doi10.1039/c8na00081pt_BR
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/61044
dc.languageengpt_BR
dc.publisherRoyal Society of Chemistrypt_BR
dc.relation.ispartofNanoscale Advancesen
dc.rightsAcesso abertopt_BR
dc.subjectUltrasmall nanoparticlesen
dc.subjectEnzyme inhibitionen
dc.titleAllosteric inhibition of a-thrombin enzymatic activity with ultrasmall gold nanoparticlesen
dc.typeArtigopt_BR
unifesp.campusEscola Paulista de Medicina (EPM)pt_BR
unifesp.departamentoBioquímicapt_BR
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