View source for 4hyt


==Na,K-ATPase in the E2P state with bound ouabain and Mg2+ in the cation-binding site==
<StructureSection load='4hyt' size='340' side='right'caption='[[4hyt]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hyt]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HYT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HYT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.404&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=17F:O-[(S)-({(2R)-2,3-BIS[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL}OXY)(HYDROXY)PHOSPHORYL]-L-SERINE'>17F</scene>, <scene name='pdbligand=1AT:BETA-D-FRUCTOFURANOSYL+6-O-DECANOYL-ALPHA-D-GLUCOPYRANOSIDE'>1AT</scene>, <scene name='pdbligand=1DS:1-O-DECANOYL-BETA-D-TAGATOFURANOSYL+BETA-D-ALLOPYRANOSIDE'>1DS</scene>, <scene name='pdbligand=CE1:O-DODECANYL+OCTAETHYLENE+GLYCOL'>CE1</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OBN:OUABAIN'>OBN</scene>, <scene name='pdbligand=PHD:ASPARTYL+PHOSPHATE'>PHD</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hyt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hyt OCA], [https://pdbe.org/4hyt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hyt RCSB], [https://www.ebi.ac.uk/pdbsum/4hyt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hyt ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AT1A1_PIG 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.
<div style="background-color:#fffaf0;">
== 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<ref>PMID:23776223</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4hyt" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Fedosova NU]]
[[Category: Laursen M]]
[[Category: Nissen P]]
[[Category: Yatime L]]