View source for 7w49


==Crystal structure of the gastric proton pump complexed with soraprazan==
<StructureSection load='7w49' size='340' side='right'caption='[[7w49]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7w49]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7W49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7W49 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]] 3.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8CE:(7~{R},8~{R},9~{R})-7-(2-methoxyethoxy)-2,3-dimethyl-9-phenyl-7,8,9,10-tetrahydroimidazo[1,2-h][1,7]naphthyridin-8-ol'>8CE</scene>, <scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</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=7w49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7w49 OCA], [https://pdbe.org/7w49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7w49 RCSB], [https://www.ebi.ac.uk/pdbsum/7w49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7w49 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ATP4A_PIG ATP4A_PIG] Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
As specific inhibitors of the gastric proton pump, responsible for gastric acidification, K(+)-competitive acid blockers (P-CABs) have recently been utilized in the clinical treatment of gastric acid-related diseases in Asia. However, as these compounds have been developed based on phenotypic screening, their detailed binding poses are unknown. We show crystal and cryo-EM structures of the gastric proton pump in complex with four different P-CABs, tegoprazan, soraprazan, PF-03716556 and revaprazan, at resolutions reaching 2.8 A. The structures describe molecular details of their interactions and are supported by functional analyses of mutations and molecular dynamics simulations. We reveal that revaprazan has a novel binding mode in which its tetrahydroisoquinoline moiety binds deep in the cation transport conduit. The mechanism of action of these P-CABs can now be evaluated at the molecular level, which will facilitate the rational development and improvement of currently available P-CABs to provide better treatment of acid-related gastrointestinal diseases.

Structural Basis for Binding of Potassium-Competitive Acid Blockers to the Gastric Proton Pump.,Tanaka S, Morita M, Yamagishi T, Madapally HV, Hayashida K, Khandelia H, Gerle C, Shigematsu H, Oshima A, Abe K J Med Chem. 2022 Jun 9;65(11):7843-7853. doi: 10.1021/acs.jmedchem.2c00338. Epub , 2022 May 23. PMID:35604136<ref>PMID:35604136</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7w49" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Abe K]]
[[Category: Tanaka S]]