tailieunhanh - Báo cáo khóa học: Binding analyses between Human PPARc–LBD and ligands Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking

The binding characteristics of a series of PPARcligands (GW9662, GI 262570, cis-parinaric acid, 15-deoxy-D 12,14 -prostaglandin J2 , LY171883, indomethacin, linoleic acid, palmitic acid and troglitazone) to human PPARcligand binding domain have been investigated for the first time by using surface plasmon resonance biosensor technology, CD spectroscopyandmoleculardockingsimulation. | Eur. J. Biochem. 271 386-397 2004 FEBS 2003 doi Binding analyses between Human PPARy-LBD and ligands Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking I B B B B B BBB BB B B BB Bb1 2 bIb BB B B 1 I I OB B I B B B B BB I B B 1 I B B B BB I B BB B B 1 BB B B BB 1 I B B B B B B I B B B B B B B B 1 B B B I B BB B I B B B B B BB 1 Changying Yu Lili Chen Haibing Luo Jing Chen Feng Cheng Chunshan GUI Ruihao Zhang Jianhua Shen1 Kaixian Chen1 Hualiang Jiang1 and Xu Shen1 1Drug Discovery and Design Center State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China 2College of Marine Life Sciences Ocean University of China Qingdao China The binding characteristics of a series of PPARy ligands GW9662 GI 262570 czs-parinaric acid 15-deoxy-A12 14-prostaglandin J2 LY171883 indomethacin linoleic acid palmitic acid and troglitazone to human PPARy ligand binding domain have been investigated for the first time by using surface plasmon resonance biosensor technology CD spectroscopy and molecular docking simulation. The surface plasmon resonance biosensor determined equilibrium dissociation constants KD values are in agreement with the results reported in the literature measured by other methods indicating that the surface plasmon resonance biosensor can assume a direct assay method in screening new PPARy agonists or antagonists. Conformational changes of PPARy caused by the ligand binding were detected by CD determination. It is interesting that the thermal stability of the receptor reflected by the increase of the transition temperature Tm was enhanced by the binding of the ligands. The increment of the transition temperature ATm of PPARy owing to ligand binding correlated well with the binding affinity. This finding implies that CD could possibly be a complementary .