3A3Y

Crystal structure of the sodium-potassium pump with bound potassium and ouabain

Summary for 3A3Y

• Entry DOI: 10.2210/pdb3a3y/pdb
• Related: 2ZXE
• Descriptor: Na, K-ATPase alpha subunit, NA+,K+-ATPASE BETA SUBUNIT, Phospholemman-like protein, ... (10 entities in total)
• Functional Keywords: membrane protein, ion pump, atpase, k+ binding, ouabain binding, haloacid dehydrogenease superfamily, phosphate analogue, atp-binding, hydrolase, ion transport, nucleotide-binding, phosphoprotein, hydrolase-transport protein complex, membrane, transmembrane, transport, hydrolase/transport protein
• Biological source: Squalus acanthias (Spiny dogfish); More
• Total number of polymer chains: 3
• Total formula weight: 158587.31

Authors

Ogawa, H.,Shinoda, T.,Cornelius, F.,Toyoshima, C. (deposition date: 2009-06-23, release date: 2009-09-08, Last modification date: 2024-11-13)

Primary citation

Ogawa, H.,Shinoda, T.,Cornelius, F.,Toyoshima, C.
Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain.
Proc.Natl.Acad.Sci.USA, 106:13742-13747, 2009

PubMed Abstract: The sodium-potassium pump (Na(+),K(+)-ATPase) is responsible for establishing Na(+) and K(+) concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials. Cardiac glycosides, prescribed for congestive heart failure for more than 2 centuries, are efficient inhibitors of this ATPase. Here we describe a crystal structure of Na(+),K(+)-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 A resolution in a state analogous to E2.2K(+).Pi. Ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K(+), in marked contrast to previous models. Due to antagonism between ouabain and K(+), the structure represents a low-affinity ouabain-bound state. Yet, most of the mutagenesis data obtained with the high-affinity state are readily explained by the present crystal structure, indicating that the binding site for ouabain is essentially the same. According to a homology model for the high affinity state, it is a closure of the binding cavity that confers a high affinity.

PubMed: 19666591
DOI: 10.1073/pnas.0907054106

Experimental method

X-RAY DIFFRACTION (2.8 Å)