Molecular Modeling of SCH28080 Binding to the Gastric H,K-ATPase and MgATP Interactions with SERCA- and Na,K-ATPases
- 1 April 2003
- journal article
- Published by Wiley in Annals of the New York Academy of Sciences
- Vol. 986 (1) , 106-110
- https://doi.org/10.1111/j.1749-6632.2003.tb07146.x
Abstract
We have used homology molecular modeling based on the srCaATPase E2 conformation, pdb1kju, to predict side chains involved in docking the K+ competitive inhibitor, SCH28080, to the H,K‐ATPase. A model for SCH28080 binding between residues L809 and A335 in the same space utilized by omeprazole is proposed. We also describe modeling MgATP binding to the E1 structure of the srATPase, pdb1eul, as a paradigm for the Na,K‐ and H,K‐ATPases. The resulting model, E1·MgATP, visualizes a conformation not yet available by crystallization and successfully predicts a range of published results, including backbone cleavages near V440 (N domain) and V712 (P domain) mediated by FeATP in the Na,K‐ATPase. A separate model for MgATP docked to E2 (pdb1kju) shows that access of the γ phosphate to D351 is blocked by the A domain. The E2· MgATP model explains FeATP‐mediated cleavages of the Na,K‐ATPase near V440 and E214 (A domain) and homologous results in the H,K‐ATPase.Keywords
This publication has 12 references indexed in Scilit:
- SCH28080, a K+-Competitive Inhibitor of the Gastric H,K-ATPase, Binds Near the M5−6 Luminal Loop, Preventing K+ Access to the Ion Binding DomainBiochemistry, 2002
- The ATP−Mg2+ Binding Site and Cytoplasmic Domain Interactions of Na+,K+-ATPase Investigated with Fe2+-Catalyzed Oxidative Cleavage and Molecular ModelingBiochemistry, 2002
- Structural changes in the calcium pump accompanying the dissociation of calciumNature, 2002
- A structural model for the catalytic cycle of Ca2+-ATPaseJournal of Molecular Biology, 2002
- Selective Fe2+-catalyzed Oxidative Cleavage of Gastric H+,K+-ATPasePublished by Elsevier ,2001
- Importance of Thr-353 of the Conserved Phosphorylation Loop of the Sarcoplasmic Reticulum Ca2+-ATPase in MgATP Binding and Catalytic ActivityJournal of Biological Chemistry, 2001
- Mutational Analysis of the K+-Competitive Inhibitor Site of Gastric H,K-ATPaseBiochemistry, 2001
- The complex ATP–Fe 2+ serves as a specific affinity cleavage reagent in ATP-Mg 2+ sites of Na,K-ATPase: Altered ligation of Fe 2+ (Mg 2+ ) ions accompanies the E 1 P→E 2 P conformational changeProceedings of the National Academy of Sciences, 2000
- Mutagenesis of Segment 487Phe-Ser-Arg-Asp-Arg-Lys492 of Sarcoplasmic Reticulum Ca2+-ATPase Produces Pumps Defective in ATP BindingPublished by Elsevier ,1996
- SCH28080 prevents omeprazole inhibition of the gastric H+/K+-ATPaseBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1988