4yay: Difference between revisions
New page: '''Unreleased structure''' The entry 4yay is ON HOLD Authors: Zhang, H., Unal, H., Gati, C., Han, G.W., Zatsepin, N.A., James, D., Wang, D., Nelson, G., Weierstall, U., Messerschmidt, M... |
No edit summary |
||
| (7 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The entry | ==XFEL structure of human Angiotensin Receptor== | ||
<StructureSection load='4yay' size='340' side='right'caption='[[4yay]], [[Resolution|resolution]] 2.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4yay]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YAY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YAY FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZD7:5,7-DIETHYL-1-{[2-(1H-TETRAZOL-5-YL)BIPHENYL-4-YL]METHYL}-3,4-DIHYDRO-1,6-NAPHTHYRIDIN-2(1H)-ONE'>ZD7</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4yay FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yay OCA], [https://pdbe.org/4yay PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yay RCSB], [https://www.ebi.ac.uk/pdbsum/4yay PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yay ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN] NON RARE IN EUROPE: Essential hypertension;Renal tubular dysgenesis of genetic origin. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.[https://www.uniprot.org/uniprot/AGTR1_HUMAN AGTR1_HUMAN] Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Angiotensin II type 1 receptor (AT1R) 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 AT1R blockers (ARBs), the structural basis for AT1R 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 AT1R in complex with its selective antagonist ZD7155 at 2.9-A resolution. The AT1R-ZD7155 complex structure revealed key structural features of AT1R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design. | |||
Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.,Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, James D, Wang D, Nelson G, Weierstall U, Sawaya MR, Xu Q, Messerschmidt M, Williams GJ, Boutet S, Yefanov OM, White TA, Wang C, Ishchenko A, Tirupula KC, Desnoyer R, Coe J, Conrad CE, Fromme P, Stevens RC, Katritch V, Karnik SS, Cherezov V Cell. 2015 May 7;161(4):833-44. doi: 10.1016/j.cell.2015.04.011. Epub 2015 Apr, 23. PMID:25913193<ref>PMID:25913193</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 4yay" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Boutet S]] | ||
[[Category: | [[Category: Cherezov V]] | ||
[[Category: | [[Category: Coe J]] | ||
[[Category: | [[Category: Cornrad CE]] | ||
[[Category: Karnik | [[Category: Desnoyer R]] | ||
[[Category: Katritch | [[Category: Fromme P]] | ||
[[Category: | [[Category: Gati C]] | ||
[[Category: | [[Category: Han GW]] | ||
[[Category: | [[Category: Ishchenko A]] | ||
[[Category: | [[Category: James D]] | ||
[[Category: | [[Category: Karnik SS]] | ||
[[Category: | [[Category: Katritch V]] | ||
[[Category: | [[Category: Liu W]] | ||
[[Category: | [[Category: Messerschmidt M]] | ||
[[Category: | [[Category: Nelson G]] | ||
[[Category: | [[Category: Sawaya MC]] | ||
[[Category: | [[Category: Stevens RC]] | ||
[[Category: | [[Category: Tirupula KC]] | ||
[[Category: | [[Category: Unal H]] | ||
[[Category: | [[Category: Wang D]] | ||
[[Category: Weierstall U]] | |||
[[Category: White TA]] | |||
[[Category: Williams GJ]] | |||
[[Category: Xu Q]] | |||
[[Category: Yefanov OM]] | |||
[[Category: Zatsepin NA]] | |||
[[Category: Zhang H]] | |||
Latest revision as of 13:07, 16 August 2023
XFEL structure of human Angiotensin ReceptorXFEL structure of human Angiotensin Receptor
Structural highlights
DiseaseAGTR1_HUMAN NON RARE IN EUROPE: Essential hypertension;Renal tubular dysgenesis of genetic origin. The disease is caused by mutations affecting the gene represented in this entry. FunctionC562_ECOLX Electron-transport protein of unknown function.AGTR1_HUMAN Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Publication Abstract from PubMedAngiotensin II type 1 receptor (AT1R) 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 AT1R blockers (ARBs), the structural basis for AT1R 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 AT1R in complex with its selective antagonist ZD7155 at 2.9-A resolution. The AT1R-ZD7155 complex structure revealed key structural features of AT1R and critical interactions for ZD7155 binding. Docking simulations of the clinically used ARBs into the AT1R structure further elucidated both the common and distinct binding modes for these anti-hypertensive drugs. Our results thereby provide fundamental insights into AT1R structure-function relationship and structure-based drug design. Structure of the Angiotensin receptor revealed by serial femtosecond crystallography.,Zhang H, Unal H, Gati C, Han GW, Liu W, Zatsepin NA, James D, Wang D, Nelson G, Weierstall U, Sawaya MR, Xu Q, Messerschmidt M, Williams GJ, Boutet S, Yefanov OM, White TA, Wang C, Ishchenko A, Tirupula KC, Desnoyer R, Coe J, Conrad CE, Fromme P, Stevens RC, Katritch V, Karnik SS, Cherezov V Cell. 2015 May 7;161(4):833-44. doi: 10.1016/j.cell.2015.04.011. Epub 2015 Apr, 23. PMID:25913193[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||