Dataset Information

Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.

ABSTRACT: Acid-related gastric diseases are associated with disorder of digestive tract acidification. The gastric proton pump, H(+),K(+)-ATPase, exports H(+) in exchange for luminal K(+) to generate a highly acidic environment in the stomach, and is a main target for acid suppressants. Here, we report the three-dimensional structure of gastric H(+),K(+)-ATPase with bound SCH28080, a representative K(+)-competitive acid blocker, at 7 Å resolution based on electron crystallography of two-dimensional crystals. The density of the bound SCH28080 is found near transmembrane (TM) helices 4, 5 and 6, in the luminal cavity. The SCH28080-binding site is formed by the rearrangement of TM helices, which is in turn transmitted to the cytoplasmic domains, resulting in a luminal-open conformation. These results represent the first structural evidence for a binding site of an acid suppressant on H(+),K(+)-ATPase, and the conformational change induced by this class of drugs.

SUBMITTER: Abe K

PROVIDER: S-EPMC3105306 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.

Abe Kazuhiro K Tani Kazutoshi K Fujiyoshi Yoshinori Y

Nature communications 20110101

Acid-related gastric diseases are associated with disorder of digestive tract acidification. The gastric proton pump, H(+),K(+)-ATPase, exports H(+) in exchange for luminal K(+) to generate a highly acidic environment in the stomach, and is a main target for acid suppressants. Here, we report the three-dimensional structure of gastric H(+),K(+)-ATPase with bound SCH28080, a representative K(+)-competitive acid blocker, at 7 Å resolution based on electron crystallography of two-dimensional crysta ...[more]

PMID: 21224846

Similar Datasets

Project description:Background The use of gastric acid suppressants (GASs) has an influence on the exposure of some epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and therefore may affect the effectiveness and safety of EGFR-TKIs. The impact of GASs, including proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), on the effectiveness and safety of EGFR-TKIs remains unclear. We conducted a meta-analysis to explore the impact of GASs on the effectiveness and safety of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients. Method We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases thoroughly from inception to 2nd February 2021, including the studies for NSCLC patients who used GASs, offering the adjusted hazard ratio (HR) of effectiveness outcomes such as overall survival (OS) and progression-free survival (PFS) or adjusted odds ratio (OR) of the adverse drug reaction (ADRs), and the results were calculated with a random effect. Two researchers independently screened the literature, extracted data, and evaluated the quality. Stata 15.0 was used for meta-analysis. Result Twelve studies were finally included. Nine of them were cohort studies, and three of them were case-control studies. For effectiveness outcomes, the use of GASs was associated with shorter PFS (HR 1.66 [1.40, 1.98]) and OS (HR 1.50 [1.31, 1.72]), and the use of PPIs was associated with shorter OS (HR 1.56 [1.21, 2.02]), regardless of the overlap time and type of EGFR-TKIs. For safety outcomes, the use of GASs (OR 1.98 [1.19, 3.31]) or PPIs (OR 1.91 [1.17, 3.12]) were both associated with an increased risk of hepatotoxicity. Conclusion The concomitant use of GASs is associated with shorter PFS and OS for NSCLC patients taking EGFR-TKIs and is also associated with a higher risk of hepatotoxicity. The co-administration of GASs should be avoided; if they cannot be avoided, H2RAs is a better choice. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021235018), identifier (PROSPERO 2021 CRD42021235018).

Dataset Information

Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.

Publications

Conformational rearrangement of gastric H(+),K(+)-ATPase induced by an acid suppressant.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets