Binding analyses between human PPAR gamma-LBD and ligands - Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking
文献类型：期刊论文
| 作者 | Yu, CY; Chen, LL ; Luo, HB; Chen, J; Cheng, F; Gui, CS; Zhang, RH; Shen, JH; Chen, KX; Jiang, HL
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| 刊名 | EUROPEAN JOURNAL OF BIOCHEMISTRY
 |
| 出版日期 | 2004-01 |
| 卷号 | 271期号:2页码:386-397 |
| 关键词 | PPAR gamma receptor binding surface plasmon resonance biosensor circular dichroism spectroscopy molecular docking |
| ISSN号 | 0014-2956 |
| DOI | 10.1046/j.1432-1033.2003.03937.x |
| 文献子类 | Article |
| 英文摘要 | The binding characteristics of a series of PPARgamma ligands (GW9662, GI 262570, cis-parinaric acid, 15-deoxy-Delta(12,14)-prostaglandin J(2), LY171883, indomethacin, linoleic acid, palmitic acid and troglitazone) to human PPARgamma 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 (K-D 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 PPARgamma agonists or antagonists. Conformational changes of PPARgamma 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 (T-m), was enhanced by the binding of the ligands. The increment of the transition temperature (DeltaT(m)) of PPARgamma owing to ligand binding correlated well with the binding affinity. This finding implies that CD could possibly be a complementary technology with which to determine the binding affinities of ligands to PPARgamma. Molecular docking simulation provided reasonable and reliable binding models of the ligands to PPARgamma at the atomic level, which gave a good explanation of the structure-binding affinity relationship for the ligands interacting with PPARgamma. Moreover, the predicted binding free energies for the ligands correlated well with the binding constants measured by the surface plasmon resonance biosensor, indicating that the docking paradigm used in this study could possibly be employed in virtual screening to discover new PPARgamma ligands, although the docking program cannot accurately predict the absolute ligand-PPARgamma binding affinity. |
| WOS关键词 | ACTIVATED RECEPTOR-GAMMA ; PROTEIN DATA-BANK ; ORBITAL ELECTRONEGATIVITY ; CRYSTAL-STRUCTURE ; ORPHAN RECEPTORS ; FATTY-ACIDS ; ALPHA ; AGONISTS ; DISCOVERY ; AGENTS |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000187958900016 |
| 出版者 | BLACKWELL PUBLISHING LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274129]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药理学第三研究室 |
| 通讯作者 | Jiang, HL |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China 2.Ocean Univ China, Coll Marine Life Sci, Qingdao, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yu, CY,Chen, LL,Luo, HB,et al. Binding analyses between human PPAR gamma-LBD and ligands - Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking[J]. EUROPEAN JOURNAL OF BIOCHEMISTRY,2004,271(2):386-397. |
| APA | Yu, CY.,Chen, LL.,Luo, HB.,Chen, J.,Cheng, F.,...&Shen, X.(2004).Binding analyses between human PPAR gamma-LBD and ligands - Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking.EUROPEAN JOURNAL OF BIOCHEMISTRY,271(2),386-397. |
| MLA | Yu, CY,et al."Binding analyses between human PPAR gamma-LBD and ligands - Surface plasmon resonance biosensor assay correlating with circular dichroic spectroscopy determination and molecular docking".EUROPEAN JOURNAL OF BIOCHEMISTRY 271.2(2004):386-397. |
入库方式： OAI收割
来源：上海药物研究所
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