Structural requirement for PPAR gamma binding revealed by a meta analysis of holo-crystal structures

Autor(es)

Nascimento, Alessandro S. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil

^[2] Univ Fed ABC, Ctr Engn Modelagem & Ciencias Sociais Aplicadas, BR-09210170 Santo Andre, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 92, n. 5, p. 499-506, MAY 2010.
• Citações Web of Science: 4

Resumo

PPAR gamma is a ligand regulated transcriptional factor that modulates the transcription of several genes involved in fat and sugar metabolism. Due to its easy bacterial expression and crystallization, several crystal structures of holo-PPAR gamma have been reported and deposited in the Protein Data Bank. Here, we investigated the three-dimensional electrostatic properties of 55 PPAR gamma ligands and used this information for clustering them through principal component analysis. We found out that, according to their electrostatic potential, these ligands can be separated in three groups, with different binding features. We also observed that non-selective and selective ligands show different 3D electrostatic properties and are separated in different clusters. The relevance of this analysis for the development of new binders is discussed. (C) 2010 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 04/08070-9 - Estudos estruturais do receptor de mineralocorticóide humano
• Beneficiário: Alessandro Silva Nascimento
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 08/58735-8 - Estudos estruturais da familia das septinas
• Beneficiário: Alessandro Silva Nascimento
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado