4YAY

XFEL structure of human Angiotensin Receptor

Summary for 4YAY

• Entry DOI: 10.2210/pdb4yay/pdb
• Descriptor: 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)
• Functional Keywords: 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
• Biological source: Escherichia coli; More
• Total number of polymer chains: 1
• Total formula weight: 47679.23

Authors

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) (deposition date: 2015-02-18, release date: 2015-04-22, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)