4ux2

Cryo-EM structure of antagonist-bound E2P gastric H,K-ATPase (SCH.E2. MgF)Cryo-EM structure of antagonist-bound E2P gastric H,K-ATPase (SCH.E2. MgF)

Structural highlights 4ux2 is a 2 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron crystallography, Resolution 7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ATP4A_PIG Catalyzes the hydrolysis of ATP coupled with the exchange of H(+) and K(+) ions across the plasma membrane. Responsible for acid production in the stomach. Publication Abstract from PubMed Gastric H+,K+-ATPase, an ATP-driven proton pump responsible for the gastric acidification, is a molecular target for anti-ulcer drugs. Here we show its cryo-electron microscopy (EM) in an E2P analog state, bound to magnesium fluoride (MgF) and its K+-competitive antagonist SCH28080, determined at 7 A resolution by electron crystallography of two-dimensional crystals. Systematic comparison with other E2P-related cryo-EM structures revealed that the molecular conformation in the (SCH)E2.MgF state is remarkably distinguishable. Although the azimuthal position of the A domain of the (SCH)E2.MgF state is similar to that in the E2.AlF (aluminum fluoride) state, in which the transmembrane luminal gate is closed, the arrangement of transmembrane helices in the (SCH)E2.MgF state shows a luminal-open conformation imposed on by bound SCH28080 at its luminal cavity, based on observations of the structure in the SCH28080-bound E2.BeF (beryllium fluoride) state. The molecular conformation of the (SCH)E2.MgF state thus represents a mixed overall structure in which its cytoplasmic and luminal half appear to be independently modulated by a phosphate analog and an antagonist bound to the respective parts of the enzyme. Comparison of the molecular conformations revealed that the linker region connecting the A domain and the transmembrane helix 2 (A-M2 linker) mediates the regulation of luminal gating. The mechanistic rationale underlying luminal gating observed in H+,K+-ATPase is consistent with that observed in sarcoplasmic reticulum Ca2+-ATPase and other P-type ATPases, and is most likely conserved for the P-type ATPase family in general. Systematic Comparison of Molecular Conformations of H+,K+-ATPase Reveals an Important Contribution of the A-M2 Linker for the Luminal Gating.,Abe K, Tani K, Fujiyoshi Y J Biol Chem. 2014 Sep 17. pii: jbc.M114.584623. PMID:25231997 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also ATPase 3D structures

spinqualitylabelsall models 4ux2, resolution 7.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image