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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Structural dataset for the PPAR gamma V290M mutant

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Autor(es):
Puhl, Ana C. [1] ; Webb, Paul [2] ; Polikarpov, Igor [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Av Trabalhador Saocarlense 400, BR-13560970 Sao Carlos, SP - Brazil
[2] Houston Methodist Res Inst, Genom Med Program, Houston, TX - USA
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: DATA IN BRIEF; v. 7, p. 1430-1437, JUN 2016.
Citações Web of Science: 1
Resumo

Loss-of-function mutation V290M in the ligand-binding domain of the peroxisome proliferator activated receptor gamma (PPAR gamma) is associated with a ligand resistance syndrome (PLRS), characterized by partial lipodystrophy and severe insulin resistance. In this data article we discuss an X-ray diffraction dataset that yielded the structure of PPAR gamma LBD V290M mutant refined at 2.3 angstrom resolution, that allowed building of 3D model of the receptor mutant with high confidence and revealed continuous well-defined electron density for the partial agonist diclofenac bound to hydrophobic pocket of the PPAR gamma. These structural data provide significant insights into molecular basis of PLRS caused by V290M mutation and are correlated with the receptor disability of rosiglitazone binding and increased affinity for corepressors. Furthermore, our structural evidence helps to explain clinical observations which point out to a failure to restore receptor function by the treatment with a full agonist of PPAR gamma, rosiglitazone. (C) 2016 The Auhtors. Published by Elsevier Inc. (AU)

Processo FAPESP: 06/00182-8 - Biofísica estrutural dos receptores nucleares e proteínas relacionadas
Beneficiário:Igor Polikarpov
Linha de fomento: Auxílio à Pesquisa - Temático