Structural requirement for PPARgamma binding revealed by a meta analysis of holo-crystal structures.
PPARgamma 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-PPARgamma have been reported and deposited in the Protein Data Bank. Here, we investigated the three-dimensional electrostatic properties of 55 PPARgamma 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.
Nascimento
Alessandro S
AS
Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador sãocarlense, 400, Centro. São Carlos, SP 13566-590, Brazil. asnascimento@if.sc.usp.br
D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015999:Multivariate Analysis; D047495:PPAR gamma / Q000737:chemistry / Q000378:metabolism*; D025341:Principal Component Analysis; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity
D047495:PPAR gamma