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5ylu
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==Crystal structure of the gastric proton pump complexed with vonoprazan== | ==Crystal structure of the gastric proton pump complexed with vonoprazan== | ||
| - | <StructureSection load='5ylu' size='340' side='right' caption='[[5ylu]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='5ylu' size='340' side='right'caption='[[5ylu]], [[Resolution|resolution]] 2.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5ylu]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YLU OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5ylu]] 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=5YLU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YLU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</scene>, <scene name='pdbligand=HKT:1-[5-(2-fluorophenyl)-1-pyridin-3-ylsulfonyl-pyrrol-3-yl]-~{N}-methyl-methanamine'>HKT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7998896Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene>, <scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</scene>, <scene name='pdbligand=HKT:1-[5-(2-fluorophenyl)-1-pyridin-3-ylsulfonyl-pyrrol-3-yl]-~{N}-methyl-methanamine'>HKT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</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=5ylu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ylu OCA], [https://pdbe.org/5ylu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ylu RCSB], [https://www.ebi.ac.uk/pdbsum/5ylu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ylu ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/ATP4B_PIG ATP4B_PIG]] Note=Parietal cell autoantigen associated with autoimmune gastritis. | ||
== Function == | == 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 == | ||
| + | The gastric proton pump-the H(+), K(+)-ATPase-is a P-type ATPase responsible for acidifying the gastric juice down to pH 1. This corresponds to a million-fold proton gradient across the membrane of the parietal cell, the steepest known cation gradient of any mammalian tissue. The H(+), K(+)-ATPase is an important target for drugs that treat gastric acid-related diseases. Here we present crystal structures of the H(+), K(+)-ATPase in complex with two blockers, vonoprazan and SCH28080, in the luminal-open state, at 2.8 A resolution. The drugs have partially overlapping but clearly distinct binding modes in the middle of a conduit running from the gastric lumen to the cation-binding site. The crystal structures suggest that the tight configuration at the cation-binding site lowers the pK a value of Glu820 sufficiently to enable the release of a proton even into the pH 1 environment of the stomach. | ||
| + | |||
| + | Crystal structures of the gastric proton pump.,Abe K, Irie K, Nakanishi H, Suzuki H, Fujiyoshi Y Nature. 2018 Apr;556(7700):214-218. doi: 10.1038/s41586-018-0003-8. Epub 2018 Apr, 4. PMID:29618813<ref>PMID:29618813</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5ylu" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[ATPase 3D structures|ATPase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Sus scrofa]] |
| - | [[Category: | + | [[Category: Abe K]] |
| - | + | [[Category: Fujiyoshi Y]] | |
| - | [[Category: | + | [[Category: Irie K]] |
| - | [[Category: | + | [[Category: Nakanishi H]] |
| - | [[Category: H | + | |
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Current revision
Crystal structure of the gastric proton pump complexed with vonoprazan
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