4hyt

Na,K-ATPase in the E2P state with bound ouabain and Mg2+ in the cation-binding site

spinqualitylabelsall models 4hyt, resolution 3.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hyt is a 6 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 17F, 1AT, 1DS, CE1, CLR, MG, NAG, OBN NonStd Res: PHD Related: 3kdp, 3n23 Activity: Sodium/potassium-exchanging ATPase, with EC number 3.6.3.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AT1A1_PIG] This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. [AT1B1_PIG] This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane. Publication Abstract from PubMed The Na(+),K(+)-ATPase maintains electrochemical gradients for Na(+) and K(+) that are critical for animal cells. Cardiotonic steroids (CTSs), widely used in the clinic and recently assigned a role as endogenous regulators of intracellular processes, are highly specific inhibitors of the Na(+),K(+)-ATPase. Here we describe a crystal structure of the phosphorylated pig kidney Na(+),K(+)-ATPase in complex with the CTS representative ouabain, extending to 3.4 A resolution. The structure provides key details on CTS binding, revealing an extensive hydrogen bonding network formed by the beta-surface of the steroid core of ouabain and the side chains of alphaM1, alphaM2, and alphaM6. Furthermore, the structure reveals that cation transport site II is occupied by Mg(2+), and crystallographic studies indicate that Rb(+) and Mn(2+), but not Na(+), bind to this site. Comparison with the low-affinity [K2]E2-MgFx-ouabain structure [Ogawa et al. (2009) Proc Natl Acad Sci USA 106(33):13742-13747) shows that the CTS binding pocket of [Mg]E2P allows deep ouabain binding with possible long-range interactions between its polarized five-membered lactone ring and the Mg(2+). K(+) binding at the same site unwinds a turn of alphaM4, dragging residues Ile318-Val325 toward the cation site and thereby hindering deep ouabain binding. Thus, the structural data establish a basis for the interpretation of the biochemical evidence pointing at direct K(+)-Mg(2+) competition and explain the well-known antagonistic effect of K(+) on CTS binding. Crystal structure of the high-affinity Na+,K+-ATPase-ouabain complex with Mg2+ bound in the cation binding site.,Laursen M, Yatime L, Nissen P, Fedosova NU Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):10958-63. doi:, 10.1073/pnas.1222308110. Epub 2013 Jun 17. PMID:23776223 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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