3FPS

The Structure of Sarcoplasmic Reticulum Ca2+-ATPase Bound To Cyclopiazonic and ADP

Summary for 3FPS

• Entry DOI: 10.2210/pdb3fps/pdb
• Descriptor: Sarcoplasmic/endoplasmic reticulum calcium ATPase 1, MAGNESIUM ION, (6AR,11AS,11BR)-10-ACETYL-9-HYDROXY-7,7-DIMETHYL-2,6,6A,7,11A,11B-HEXAHYDRO-11H-PYRROLO[1',2':2,3]ISOINDOLO[4,5,6-CD]INDOL-11-ONE, ... (5 entities in total)
• Functional Keywords: calcium-transporting atpase sarcoplasmic reticulum, fast twitch skeletal muscle isoform, endoplasmic reticulum, hydrolase
• Biological source: Oryctolagus cuniculus (Rabbit)
• Cellular location: Endoplasmic reticulum membrane ; Multi-pass membrane protein : P04191
• Total number of polymer chains: 1
• Total formula weight: 110414.77

Authors

Moncoq, K.,Morth, J.P.,Bublitz, M.,Laursen, M.,Nissen, P.,Young, H.S. (deposition date: 2009-01-06, release date: 2009-04-07, Last modification date: 2024-11-06)

Primary citation

Laursen, M.,Bublitz, M.,Moncoq, K.,Olesen, C.,Moller, J.V.,Young, H.S.,Nissen, P.,Morth, J.P.
Cyclopiazonic acid is complexed to a divalent metal ion when bound to the sarcoplasmic reticulum Ca2+-ATPase.
J.Biol.Chem., 284:13513-13518, 2009

PubMed Abstract: 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.

PubMed: 19289472
DOI: 10.1074/jbc.C900031200

Experimental method

X-RAY DIFFRACTION (3.2 Å)