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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Structural dataset for the PPAR gamma V290M mutant

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Puhl, Ana C. [1] ; Webb, Paul [2] ; Polikarpov, Igor [1]
Total Authors: 3
[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
Total Affiliations: 2
Document type: Journal article
Source: DATA IN BRIEF; v. 7, p. 1430-1437, JUN 2016.
Web of Science Citations: 1

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)

FAPESP's process: 06/00182-8 - Structural biophysics of nuclear receptors and related proteins
Grantee:Igor Polikarpov
Support type: Research Projects - Thematic Grants