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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleIdentification of a New Hormone-Binding Site on the Surface of Thyroid Hormone Receptorpt_BR
dc.contributor.authorSouza, PCTpt_BR
dc.contributor.authorPuhl, ACpt_BR
dc.contributor.authorMartinez, Lpt_BR
dc.contributor.authorAparicio, Rpt_BR
dc.contributor.authorNascimento, ASpt_BR
dc.contributor.authorFigueira, ACMpt_BR
dc.contributor.authorNguyen, Ppt_BR
dc.contributor.authorWebb, Ppt_BR
dc.contributor.authorSkaf, MSpt_BR
dc.contributor.authorPolikarpov, Ipt_BR
unicamp.author.emailipolikarpov@ifsc.usp.brpt_BR
unicamp.authorSouza, P. C. T. Martinez, L. Aparicio, R. Skaf, M. S. State Univ Campinas UNICAMP, Inst Chem, Campinas, SP, Brazilpt_BR
unicamp.authorPuhl, A. C. Nascimento, A. S. Webb, P. Polikarpov, I. Univ Sao Paulo, Inst Phys Sao Carlos, Sao Carlos, SP, Brazilpt_BR
unicamp.authorFigueira, A. C. M. CNPEM, Natl Lab Biosci, Campinas, SP, Brazilpt_BR
unicamp.authorNguyen, P. Univ Calif San Francisco, Med Ctr, Ctr Diabet, San Francisco, CA USApt_BR
unicamp.authorWebb, P. Houston Methodist Res Inst, Houston, TX USApt_BR
dc.subject.wosMolecular-dynamics Simulationspt_BR
dc.subject.wosVitamin-d-receptorpt_BR
dc.subject.wosX-ray-diffractionpt_BR
dc.subject.wos3 Bf3 Sitept_BR
dc.subject.wosLigand-bindingpt_BR
dc.subject.wosCoactivator-bindingpt_BR
dc.subject.wosEstrogen-receptorpt_BR
dc.subject.wosAndrogen Receptorpt_BR
dc.subject.wosInitial Configurationspt_BR
dc.subject.wosAntiestrogen Actionpt_BR
dc.description.abstractThyroid hormone receptors (TRs) are members of the nuclear receptor superfamily of ligand-activated transcription factors involved in cell differentiation, growth, and homeostasis. Although X-ray structures of many nuclear receptor ligand-binding domains (LBDs) reveal that the ligand binds within the hydrophobic core of the ligand-binding pocket, a few studies suggest the possibility of ligands binding to other sites. Here, we report a new x-ray crystallographic structure of TR-LBD that shows a second binding site for T-3 and T-4 located between H9, H10, and H11 of the TR alpha LBD surface. Statistical multiple sequence analysis, site-directed mutagenesis, and cell transactivation assays indicate that residues of the second binding site could be important for the TR function. We also conducted molecular dynamics simulations to investigate ligand mobility and ligand-protein interaction for T-3 and T-4 bound to this new TR surface-binding site. Extensive molecular dynamics simulations designed to compute ligand-protein dissociation constant indicate that the binding affinities to this surface site are of the order of the plasma and intracellular concentrations of the thyroid hormones, suggesting that ligands may bind to this new binding site under physiological conditions. Therefore, the second binding site could be useful as a new target site for drug design and could modulate selectively TR functions.pt
dc.description.noteo TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.pt
dc.relation.ispartofMolecular Endocrinologypt_BR
dc.relation.ispartofabbreviationMol. Endocrinol.pt_BR
dc.publisher.cityWashingtonpt_BR
dc.publisher.countryEUApt_BR
dc.publisherEndocrine Socpt_BR
dc.date.issued2014pt_BR
dc.date.monthofcirculationAPRpt_BR
dc.identifier.citationMolecular Endocrinology. Endocrine Soc, v. 28, n. 4, n. 534, n. 545, 2014.pt_BR
dc.language.isoenpt_BR
dc.description.volume28pt_BR
dc.description.issuenumber4pt_BR
dc.description.firstpage534pt_BR
dc.description.lastpage545pt_BR
dc.rightsembargopt_BR
dc.sourceWeb of Sciencept_BR
unicamp.cruespUSPpt_BR
dc.identifier.issn0888-8809pt_BR
dc.identifier.wosidWOS:000335452100010pt_BR
dc.identifier.doi10.1210/me.2013-1359pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsordocumentnumberFAPESP [2010/17048-8, 2013/08293-7]pt
dc.date.available2014-07-30T18:00:16Z
dc.date.available2015-11-26T16:49:51Z-
dc.date.accessioned2014-07-30T18:00:16Z
dc.date.accessioned2015-11-26T16:49:51Z-
dc.description.provenanceMade available in DSpace on 2014-07-30T18:00:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2014en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:49:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2014en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/69130
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/69130-
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