Allosteric Pathways In The Ppar Gamma-rxr Alpha Nuclear Receptor Complex

dc.creatorRicci
dc.creatorClarisse G.; Silveira
dc.creatorRodrigo L.; Rivalta
dc.creatorIvan; Batista
dc.creatorVictor S.; Skaf
dc.creatorMunir S.
dc.date2016-Jan
dc.date2016-06-07T13:22:44Z
dc.date2016-06-07T13:22:44Z
dc.date.accessioned2018-03-29T01:42:17Z
dc.date.available2018-03-29T01:42:17Z
dc.identifier
dc.identifierAllosteric Pathways In The Ppar Gamma-rxr Alpha Nuclear Receptor Complex. Nature Publishing Group, v. 6, p. Jan-2016.
dc.identifier2045-2322
dc.identifierWOS:000368927800001
dc.identifier10.1038/srep19940
dc.identifierhttp://www.nature.com/articles/srep19940
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/243250
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1306948
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionUnderstanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Omega-loops and PPAR gamma-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors.
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dc.description
dc.description
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionNational Institute of Health (NIH) [1R01GM10621-01A1]
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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dc.description
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dc.languageen
dc.publisherNATURE PUBLISHING GROUP
dc.publisher
dc.publisherLONDON
dc.relationSCIENTIFIC REPORTS
dc.rightsaberto
dc.sourceWOS
dc.subjectProliferator-activated Receptors
dc.subjectLigand-binding Domain
dc.subjectMolecular-dynamics
dc.subjectSignaling Pathways
dc.subjectEnergy Landscapes
dc.subjectBackbone Dynamics
dc.subjectOrphan Receptors
dc.subjectFatty-acids
dc.subjectDna
dc.subjectProteins
dc.titleAllosteric Pathways In The Ppar Gamma-rxr Alpha Nuclear Receptor Complex
dc.typeArtículos de revistas


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