5ylv: Difference between revisions
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<StructureSection load='5ylv' size='340' side='right' caption='[[5ylv]], [[Resolution|resolution]] 2.80Å' scene=''> | <StructureSection load='5ylv' size='340' side='right' caption='[[5ylv]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ylv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YLV FirstGlance]. <br> | <table><tr><td colspan='2'>[[5ylv]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YLV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YLV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WX:2-(2-methyl-8-phenylmethoxy-imidazo[1,2-a]pyridin-3-yl)ethanenitrile'>8WX</scene>, <scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</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>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8WX:2-(2-methyl-8-phenylmethoxy-imidazo[1,2-a]pyridin-3-yl)ethanenitrile'>8WX</scene>, <scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</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>, <scene name='pdbligand=RB:RUBIDIUM+ION'>RB</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=BFD:ASPARTATE+BERYLLIUM+TRIFLUORIDE'>BFD</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ATP4A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG]), ATP4B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrogen/potassium-exchanging_ATPase Hydrogen/potassium-exchanging ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.10 3.6.3.10] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydrogen/potassium-exchanging_ATPase Hydrogen/potassium-exchanging ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.10 3.6.3.10] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ylv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ylv OCA], [http://pdbe.org/5ylv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ylv RCSB], [http://www.ebi.ac.uk/pdbsum/5ylv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ylv ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ylv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ylv OCA], [http://pdbe.org/5ylv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ylv RCSB], [http://www.ebi.ac.uk/pdbsum/5ylv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ylv ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://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. | [[http://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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5ylv" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Hydrogen/potassium-exchanging ATPase]] | [[Category: Hydrogen/potassium-exchanging ATPase]] | ||
[[Category: Pig]] | |||
[[Category: Abe, K]] | [[Category: Abe, K]] | ||
[[Category: Fujiyoshi, Y]] | [[Category: Fujiyoshi, Y]] | ||
Revision as of 09:42, 18 April 2018
Crystal structure of the gastric proton pump complexed with SCH28080Crystal structure of the gastric proton pump complexed with SCH28080
Structural highlights
Disease[ATP4B_PIG] Note=Parietal cell autoantigen associated with autoimmune gastritis. Function[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. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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