3FPS: The Structure Of Sarcoplasmic Reticulum Ca2+-atpase Bound To Cyclopiazonic And Adp

We have determined the structure of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) in an E2.P(i)-like form stabilized as a complex with MgF(4)(2-), an ATP analog, adenosine 5'-(beta,gamma-methylene)triphosphate (AMPPCP), and cyclopiazonic acid (CPA). The structure determined at 2.5A resolution leads to a significantly revised model of CPA binding when compared with earlier reports. It shows that a divalent metal ion is required for CPA binding through coordination of the tetramic acid moiety at a characteristic kink of the M1 helix found in all P-type ATPase structures, which is expected to be part of the cytoplasmic cation access pathway. Our model is consistent with the biochemical data on CPA function and provides new measures in structure-based drug design targeting Ca(2+)-ATPases, e.g. from pathogens. We also present an extended structural basis of ATP modulation pinpointing key residues at or near the ATP binding site. A structural comparison to the Na(+),K(+)-ATPase reveals that the Phe(93) side chain occupies the equivalent binding pocket of the CPA site in SERCA, suggesting an important role of this residue in stabilization of the potassium-occluded E2 state of Na(+),K(+)-ATPase.
PDB ID: 3FPSDownload
MMDB ID: 70711
PDB Deposition Date: 2009/1/6
Updated in MMDB: 2017/08
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Similar Structures:
Biological Unit for 3FPS: monomeric; determined by author and by software (PISA)
Molecular Components in 3FPS
Label Count Molecule
Protein (1 molecule)
Sarcoplasmic/endoplasmic Reticulum Calcium Atpase 1(Gene symbol: ATP2A1)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB