Antagonist binding and induced conformational dynamics of GPCR A(2A) adenosine receptor
文献类型：期刊论文
| 作者 | Pang, Xueqin; Yang, Mingjun; Han, Keli |
| 刊名 | proteins-structure function and bioinformatics
 |
| 出版日期 | 2013-08-01 |
| 卷号 | 81期号:8页码:1399-1410 |
| 关键词 | A(2A)AR molecular dynamics ZM241385 KW6002 ligand specific binding ionic lock rotamer toggle switch secondary structure |
| 英文摘要 | the a(2a) adenosine receptor (a(2a)ar) is a unique g-protein coupled receptor (gpcr), because besides agonist, its antagonist could also lead to therapeutic relevance. based on a(2a)ar-antagonist crystal structure, we have studied the binding mechanism of two distinct antagonists, zm241385 and kw6002, and dynamic behaviors of a(2a)ar induced by antagonist binding. key residues interacting with both antagonists and residues specifically binding to one of them are identified. zm241385 specifically bound to s67(2.65), m177(5.38), and n253(6.55), while kw6002 binds to f62(2.60), a81(3.29), and h264(7.29). moreover, interactions with l167(5.28) are found for both antagonists, which were not reported in agonist binding. the dynamic behaviors of antagonist bound holo-a(2a)ars were found to be different from the apo-a(2a)ar in three typical functional switches, (i) the ionic lock was in equilibrium between formation and breakage in apo-a(2a)ar, but stayed broken in holo-a(2a)ars; (ii) the rotamer toggle switch, t88(3.36)/f242(6.44)/w246(6.48), adopted different rotameric conformations in apo-a(2a)ar and holo-a(2a)ars; (iii) apo-a(2a)ar preferred -helical intracellular loop (ic)2 and flexible ic3, while holo-a(2a)ars had a flexible ic2 and -helical ic3. our results indicated that antagonist binding induced different conformational rearrangements of these characteristic functional switches in apo-a(2a)ar and holo-a(2a)ars. proteins 2013; 81:1399-1410. (c) 2013 wiley periodicals, inc. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 类目[WOS] | biochemistry & molecular biology ; biophysics |
| 研究领域[WOS] | biochemistry & molecular biology ; biophysics |
| 关键词[WOS] | protein-coupled receptor ; angstrom crystal-structure ; molecular-dynamics ; transmembrane helices ; muscarinic receptor ; parkinsons-disease ; intracellular loop ; rhodopsin ; activation ; dopamine |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000329220400010 |
| 公开日期 | 2015-11-10 |
| 源URL | [http://159.226.238.44/handle/321008/137928]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Liaoning, Peoples R China |
| 推荐引用方式 GB/T 7714 | Pang, Xueqin,Yang, Mingjun,Han, Keli. Antagonist binding and induced conformational dynamics of GPCR A(2A) adenosine receptor[J]. proteins-structure function and bioinformatics,2013,81(8):1399-1410. |
| APA | Pang, Xueqin,Yang, Mingjun,&Han, Keli.(2013).Antagonist binding and induced conformational dynamics of GPCR A(2A) adenosine receptor.proteins-structure function and bioinformatics,81(8),1399-1410. |
| MLA | Pang, Xueqin,et al."Antagonist binding and induced conformational dynamics of GPCR A(2A) adenosine receptor".proteins-structure function and bioinformatics 81.8(2013):1399-1410. |
入库方式： OAI收割
来源：大连化学物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。