标题：Exploring the Effect of Tyrosine 473 Point Mutations on the Interactions Between Peroxisome Proliferator-Activated Receptor-gamma and Rosiglitazone
作者：Liu, Mengyuan; Wang, Lushan; Zhao, Xian; Sun, Xun
作者机构：[Liu, Mengyuan; Zhao, Xian; Sun, Xun] Shandong Univ, State Key Lab Crystal Mat, Jinan 250100, Peoples R China.; [Wang, Lushan] Shandong Univ, State 更多
通讯作者地址：[Zhao, X]Shandong Univ, State Key Lab Crystal Mat, Jinan 250100, Peoples R China.
来源：LATIN AMERICAN JOURNAL OF PHARMACY
关键词：Agonist; Molecular dynamics; Type II diabetes
摘要：The peroxisome proliferator-activated receptor-gamma ( PPAR-gamma) is a ligand-dependent transcription factor which is important in adipocyte differentiation and glucose homeostasis. Rosiglitazone is a PPAR-gamma agonist and has been used to treat type II diabetes. The aim of this work is to determine the residues which interact with rosiglitazone could be affected by Y473 point mutations. To achieve this, molecular dynamics simulations of wild type PPAR-gamma/rosiglitazone/coactivator complex and its two mutants were carried out. Results show that apart from residue 473, point mutations have influence on the interactions of rosiglitazone with some other residues and lead to reduced agonist binding and transcriptional activity. It is hoped that this information would be helpful for medicinal chemists to design potent PPAR-gamma agonists.