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6nsj

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Revision as of 10:36, 4 December 2019

CryoEM structure of Helicobacter pylori urea channel in closed state

Structural highlights

6nsj is a 6 chain structure with sequence from Campylobacter pylori j99. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	ureI, jhp_0066 (Campylobacter pylori J99)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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).

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Cui Y, Zhou K, Strugatsky D, Wen Y, Sachs G, Zhou ZH, Munson K. pH-dependent gating mechanism of the Helicobacter pylori urea channel revealed by cryo-EM. Sci Adv. 2019 Mar 20;5(3):eaav8423. doi: 10.1126/sciadv.aav8423. eCollection 2019, Mar. PMID:30906870 doi:http://dx.doi.org/10.1126/sciadv.aav8423

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6nsj"

@@ Line 3: / Line 3: @@
 <StructureSection load='6nsj' size='340' side='right'caption='[[6nsj]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nsj]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NSJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nsj]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Campylobacter_pylori_j99 Campylobacter pylori j99]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NSJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NSJ 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ureI, jhp_0066 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=85963 Campylobacter pylori J99])</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=6nsj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nsj OCA], [http://pdbe.org/6nsj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nsj RCSB], [http://www.ebi.ac.uk/pdbsum/6nsj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nsj ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Campylobacter pylori j99]]
 [[Category: Large Structures]]
 [[Category: Cui, Y X]]

6nsj

From Proteopedia

Revision as of 10:36, 4 December 2019

CryoEM structure of Helicobacter pylori urea channel in closed state

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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