6nsk
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==CryoEM structure of Helicobacter pylori urea channel in open state.== | |
| + | <StructureSection load='6nsk' size='340' side='right'caption='[[6nsk]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6nsk]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NSK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NSK FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=XP4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHATE'>XP4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6nsj|6nsj]]</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=6nsk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nsk OCA], [http://pdbe.org/6nsk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nsk RCSB], [http://www.ebi.ac.uk/pdbsum/6nsk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nsk ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/UREI_HELPJ UREI_HELPJ]] Functions as a specific, H(+)-activated urea channel that increases the rate of urea entry into the cytoplasm, resulting in activation of cytoplasmic urease at acidic medium pH. Is essential for H.pylori gastric survival and colonization. Is necessary for the adaptation of urease activity to the extracellular pH, as in the presence of urea, UreI rapidly enhances the production of ammonia in the extracellular medium when the pH of the medium was decreased to pH5 or below (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The urea channel of Helicobacter pylori (HpUreI) is an ideal drug target for preventing gastric cancer but incomplete understanding of its gating mechanism has hampered development of inhibitors for the eradication of H. pylori. Here, we present the cryo-EM structures of HpUreI in closed and open conformations, both at a resolution of 2.7 A. Our hexameric structures of this small membrane protein (~21 kDa/protomer) resolve its periplasmic loops and carboxyl terminus that close and open the channel, and define a gating mechanism that is pH dependent and requires cooperativity between protomers in the hexamer. Gating is further associated with well-resolved changes in the channel-lining residues that modify the shape and length of the urea pore. Site-specific mutations in the periplasmic domain and urea pore identified key residues important for channel function. Drugs blocking the urea pore based on our structures should lead to a new strategy for H. pylori eradication. | ||
| - | + | pH-dependent gating mechanism of the Helicobacter pylori urea channel revealed by cryo-EM.,Cui Y, Zhou K, Strugatsky D, Wen Y, Sachs G, Zhou ZH, Munson K Sci Adv. 2019 Mar 20;5(3):eaav8423. doi: 10.1126/sciadv.aav8423. eCollection 2019, Mar. PMID:30906870<ref>PMID:30906870</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6nsk" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Cui, Y X]] | ||
| + | [[Category: Munson, K]] | ||
| + | [[Category: Sachs, G]] | ||
| + | [[Category: Strugatsky, D]] | ||
| + | [[Category: Wen, Y]] | ||
| + | [[Category: Zhou, K]] | ||
| + | [[Category: Zhou, Z H]] | ||
| + | [[Category: Helicobacter pylori]] | ||
| + | [[Category: Open state]] | ||
| + | [[Category: Transport protein]] | ||
| + | [[Category: Urea channel]] | ||
Revision as of 07:09, 3 April 2019
CryoEM structure of Helicobacter pylori urea channel in open state.
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