4YAY

XFEL structure of human Angiotensin Receptor

4YAY の概要

• エントリーDOI: 10.2210/pdb4yay/pdb
• 分子名称: Soluble cytochrome b562,Type-1 angiotensin II receptor, 5,7-diethyl-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-3,4-dihydro-1,6-naphthyridin-2(1H)-one (2 entities in total)
• 機能のキーワード: xfel, serial femtosecond crystallography, human angiotensin receptor at1r, bril, g protein-coupled receptor, gpcr, gpcr network, lipidic cubic phase, lcp, membrane protein, structural genomics, zd7155, angiotensin receptor blocker, room temperature, psi-biology
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47679.23

構造登録者

Zhang, H.,Unal, H.,Gati, C.,Han, G.W.,Zatsepin, N.A.,James, D.,Wang, D.,Nelson, G.,Weierstall, U.,Messerschmidt, M.,Williams, G.J.,Boutet, S.,Yefanov, O.M.,White, T.A.,Liu, W.,Ishchenko, A.,Tirupula, K.C.,Desnoyer, R.,Sawaya, M.C.,Xu, Q.,Coe, J.,Cornrad, C.E.,Fromme, P.,Stevens, R.C.,Katritch, V.,Karnik, S.S.,Cherezov, V.,GPCR Network (GPCR) (登録日: 2015-02-18, 公開日: 2015-04-22, 最終更新日: 2024-10-23)

主引用文献

Zhang, H.,Unal, H.,Gati, C.,Han, G.W.,Liu, W.,Zatsepin, N.A.,James, D.,Wang, D.,Nelson, G.,Weierstall, U.,Sawaya, M.R.,Xu, Q.,Messerschmidt, M.,Williams, G.J.,Boutet, S.,Yefanov, O.M.,White, T.A.,Wang, C.,Ishchenko, A.,Tirupula, K.C.,Desnoyer, R.,Coe, J.,Conrad, C.E.,Fromme, P.,Stevens, R.C.,Katritch, V.,Karnik, S.S.,Cherezov, V.
Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.
Cell, 161:833-844, 2015

PubMed Abstract: Angiotensin II type 1 receptor (AT(1)R) is a G protein-coupled receptor that serves as a primary regulator for blood pressure maintenance. Although several anti-hypertensive drugs have been developed as AT(1)R blockers (ARBs), the structural basis for AT(1)R ligand-binding and regulation has remained elusive, mostly due to the difficulties of growing high-quality crystals for structure determination using synchrotron radiation. By applying the recently developed method of serial femtosecond crystallography at an X-ray free-electron laser, we successfully determined the room-temperature crystal structure of the human AT(1)R in complex with its selective antagonist ZD7155 at 2.9-Å resolution. The AT(1)R-ZD7155 complex structure revealed key structural features of AT(1)R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT(1)R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT(1)R structure-function relationship and structure-based drug design.

PubMed: 25913193
DOI: 10.1016/j.cell.2015.04.011

実験手法

X-RAY DIFFRACTION (2.9 Å)