Abstract

This is a new application from an established investigator to investigate structure function relationships of the H+,K+ ATPase. This PI proposes to investigate a new class of acid suppressant medication, imidazo-1,2alpha-pyridnes, which are non-covalent inhibitors of the enzyme. The potential binding sites of SCH28080 and other imidazo-pyridines will be investigated by kinetic measurements in cells transfected with the H+,K+ ATPase and mutated enzyme. Specific membrane segments involved in recognition of this class of inhibitors will be identified. Models will largely rely on the recently identified crystal structure of sr Ca ATPase and Neurospora H+ ATPases, thus the current proposal will refine the model that currently is proposed and maybe used to generate structure-function data for understanding the ion transport role of H+,K+ ATPase and its regulation by this new class of acid suppressant drugs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK058333-01
Application #
6191418
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Hamilton, Frank A
Project Start
2000-09-15
Project End
2005-08-31
Budget Start
2000-09-15
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$249,480
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Physiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Sachs, G; Marcus, E A; Wen, Y et al. (2018) Editorial: control of acid secretion. Aliment Pharmacol Ther 48:682-683
Wen, Yi; Scott, David R; Vagin, Olga et al. (2018) Measurement of Internal pH in Helicobacter pylori by Using Green Fluorescent Protein Fluorimetry. J Bacteriol 200:
Wen, Yi; Feng, Jing; Sachs, George (2013) Helicobacter pylori 5'ureB-sRNA, a cis-encoded antisense small RNA, negatively regulates ureAB expression by transcription termination. J Bacteriol 195:444-52
Strugatsky, David; McNulty, Reginald; Munson, Keith et al. (2013) Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori. Nature 493:255-8
Tokhtaeva, Elmira; Clifford, Rebecca J; Kaplan, Jack H et al. (2012) Subunit isoform selectivity in assembly of Na,K-ATPase ?-? heterodimers. J Biol Chem 287:26115-25
Tokhtaeva, Elmira; Sachs, George; Sun, Haiying et al. (2012) Identification of the amino acid region involved in the intercellular interaction between the *1 subunits of Na+/K+ -ATPase. J Cell Sci 125:1605-16
Goebel, M; Stengel, A; Lambrecht, N W G et al. (2011) Selective gene expression by rat gastric corpus epithelium. Physiol Genomics 43:237-54
Shin, Jai Moo; Munson, Keith; Sachs, George (2011) Gastric H+,K+-ATPase. Compr Physiol 1:2141-53
Shin, J M; Vagin, O; Munson, K et al. (2011) Erratum to: Molecular mechanisms in therapy of acid-related diseases. Cell Mol Life Sci 68:921
Shin, Jai Moo; Inatomi, Nobuhiro; Munson, Keith et al. (2011) 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). J Pharmacol Exp Ther 339:412-20

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