ArticleBiochemistry2007
Analysis of the gastric H,K ATPase for ion pathways and inhibitor binding sites.
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.
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Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Gastric proton pump with two occluded KNature communications · 2021Article
- KScientific reports · 2018Article
- The cryo-EM structure of gastric HScientific reports · 2017Article
- Computational insights into the interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives with H(+),K(+)-ATPase at different pH.Journal of computer-aided molecular design · 2016Article
- The binding selectivity of vonoprazan (TAK-438) to the gastric H+, K+ -ATPase.Alimentary pharmacology & therapeutics · 2015Article
- Article
- ATP4A gene regulatory network for fine-tuning of proton pump and ion channels.Systems and synthetic biology · 2013Article
- Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438).The Journal of pharmacology and experimental therapeutics · 2011Article
- Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.Nature communications · 2011Article
- Update on the mechanisms of gastric acid secretion.Current gastroenterology reports · 2010Review
- The renal H+-K+-ATPases: physiology, regulation, and structure.American journal of physiology. Renal physiology · 2010Review
- The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K-ATPase.Pflugers Archiv : European journal of physiology · 2009Article
- The gastric HK-ATPase: structure, function, and inhibition.Pflugers Archiv : European journal of physiology · 2009Review
- Pharmacology of proton pump inhibitors.Current gastroenterology reports · 2008Review
- Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritis.European journal of immunology · 2008Article
- An ion gating mechanism of gastric H,K-ATPase based on molecular dynamics simulations.Biophysical journal · 2008Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
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].
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Registered trials
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.