Evidence map›Paper›PMID 17425287›Full record

ArticleBiochemistry2007

Analysis of the gastric H,K ATPase for ion pathways and inhibitor binding sites.

Keith Munson, Richard J Law, George Sachs

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.3field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 37 citations in OpenAlex.

  1. Gastric proton pump with two occluded KNature communications · 2021
    Article
  2. KScientific reports · 2018
    Article
  3. The cryo-EM structure of gastric HScientific reports · 2017
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Update on the mechanisms of gastric acid secretion.Current gastroenterology reports · 2010
    Review
  11. The renal H+-K+-ATPases: physiology, regulation, and structure.American journal of physiology. Renal physiology · 2010
    Review
  12. Article
  13. The gastric HK-ATPase: structure, function, and inhibition.Pflugers Archiv : European journal of physiology · 2009
    Review
  14. Pharmacology of proton pump inhibitors.Current gastroenterology reports · 2008
    Review
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Keith MunsonLaboratory of Membrane Biology, David Geffen School of Medicine at UCLA, and VA GLAHS, Los Angeles, California 90073, USA. kmunson@ucla.edu
Richard J Law
George Sachs
Lawrence Livermore National Laboratory · USVA Greater Los Angeles Healthcare System · US

Funding

The Gastric Biology of Helicobacter PyloriR01DK053642 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SACHS, GEORGE · 1997 to 2012
$3.2M
THE GASTRIC ACID PUMP AS A TARGET FOR ULCER TREATMENTR01DK058333 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SACHS, GEORGE · 2000 to 2009
$2.6M
GASTRIC ENTEROCHROMAFFIN-LIKE CELL IN ULCER DISEASER01DK046917 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SACHS, GEORGE · 1994 to 2005
$798k
The Gastric Acid Pump as a Target for Ulcer TreatmentR56DK058333 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SACHS, GEORGE · 2010 to 2010
$229k
SIMIAN RETROVIRUSES--NOVEL GENE DELIVERY VECTORSR21DK053462 · NIDDK · OREGON REGIONAL PRIMATE RESEARCH CENTER · PI MACHIDA, CURTIS A · 1998 to 1999
–
NIDDK NIH HHS DK46917NIDDK NIH HHS DK53462NIDDK NIH HHS DK58333NIDDK NIH HHS R01 DK046917NIDDK NIH HHS R01 DK053642NIDDK NIH HHS R01 DK058333NIDDK NIH HHS R56 DK058333
6 · The paper itself

Abstract

New models of the gastric H,K ATPase in the E1K and E2P states are presented as the first structures of a K+ counter-transport P2-type ATPase exhibiting ion entry and exit paths. Homology modeling was first used to generate a starting conformation from the srCa ATPase E2P form (PDB code 1wpg) that contains bound MgADP. Energy minimization of the model showed a conserved adenosine site but nonconserved polyphosphate contacts compared to the srCa ATPase. Molecular dynamics was then employed to expand the luminal entry sufficiently to allow access of the rigid K+ competitive naphthyridine inhibitor, Byk99, to its binding site within the membrane domain. The new E2P model had increased separation between transmembrane segments M3 through M8, and addition of water in this space showed not only an inhibitor entry path to the luminal vestibule but also a channel leading to the ion binding site. Addition of K+ to the hydrated channel with molecular dynamics modeling of ion movement identified a pathway for K+ from the lumen to the ion binding site to give E2K. A K+ exit path to the cytoplasm operating during the normal catalytic cycle is also proposed on the basis of an E1K homology model derived from the E12Ca2+ form of the srCa ATPase (PDB code 1su4). Autodock analyses of the new E2P model now correctly discriminate between high- and low-affinity K+ competitive inhibitors. Finally, the expanded luminal vestibule of the E2P model explains high-affinity ouabain binding in a mutant of the H,K ATPase [Qiu et al. (2005) J. Biol. Chem. 280, 32349-32355].

Indexed as

Amino Acid SubstitutionAnimalsBinding, CompetitiveBinding SitesComputer SimulationEnzyme InhibitorsGastric MucosaH(+)-K(+)-Exchanging ATPaseIon TransportModels, MolecularProtein ConformationProton Pump InhibitorsRabbitsRatsSequence Homology, Amino AcidSignal TransductionEnzyme InhibitorsH(+)-K(+)-Exchanging ATPaseProton Pump Inhibitors

Identifiers

PMID17425287
PMCPMC2837483
OpenAlexW2093758154

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.