3N23: Crystal Structure Of The High Affinity Complex Between Ouabain And The E2p Form Of The Sodium-potassium Pump

The Na+,K+-ATPase belongs to the P-ATPase family, whose characteristic property is the formation of a phosphorylated intermediate. The enzyme is also a defined target for cardiotonic steroids which inhibit its functional activity and initiate intracellular signaling. Here we describe the 4.6 A resolution crystal structure of the pig kidney Na+,K+-ATPase in its phosphorylated form stabilized by high affinity binding of the cardiotonic steroid ouabain. The steroid binds to a site formed at transmembrane segments alphaM1-alphaM6, plugging the ion pathway from the extracellular side. This structure differs from the previously reported low affinity complex with potassium. Most importantly, the A domain has rotated in response to phosphorylation and alphaM1-2 move towards the ouabain molecule, providing for high affinity interactions and closing the ion pathway from the extracellular side. The observed re-arrangements of the Na+,K+-ATPase stabilized by cardiotonic steroids may affect protein-protein interactions within the intracellular signal transduction networks.
PDB ID: 3N23Download
MMDB ID: 88043
PDB Deposition Date: 2010/5/17
Updated in MMDB: 2014/09
Experimental Method:
x-ray diffraction
Resolution: 4.6  Å
Source Organism:
Similar Structures:
Biological Unit for 3N23: trimeric; determined by author and by software (PISA)
Molecular Components in 3N23
Label Count Molecule
Proteins (3 molecules)
Sodium/potassium-transporting Atpase Subunit Alpha-1(Gene symbol: ATP1A1)
Molecule annotation
Sodium/potassium-transporting Atpase Subunit Beta-1(Gene symbol: ATP1B1)
Molecule annotation
Na+/k+ Atpase Gamma Subunit Transcript Variant a
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB