3FGO

Crystal Structure of the E2 magnesium fluoride complex of the (SR) Ca2+-ATPase with bound CPA and AMPPCP

Summary for 3FGO

• Entry DOI: 10.2210/pdb3fgo/pdb
• Descriptor: Sarcoplasmic/endoplasmic reticulum calcium ATPase 1, MAGNESIUM ION, TETRAFLUOROMAGNESATE(2-), ... (9 entities in total)
• Functional Keywords: calcium pump, serca, nonhydrolyzable atp analog, p-type-atpase, phosphorylation, cyclopiazonic acid, cpa, alternative splicing, atp-binding, calcium, calcium transport, endoplasmic reticulum, hydrolase, ion transport, magnesium, membrane, metal-binding, nucleotide-binding, phosphoprotein, sarcoplasmic reticulum, transmembrane, transport
• Biological source: Oryctolagus cuniculus (Rabbit)
• Cellular location: Endoplasmic reticulum membrane; Multi-pass membrane protein: P04191
• Total number of polymer chains: 2
• Total formula weight: 221616.73

Authors

Laursen, M.,Bublitz, M.,Moncoq, K.,Olesen, C.,Moller, J.V.,Young, H.S.,Nissen, P.,Morth, J.P. (deposition date: 2008-12-08, release date: 2009-04-07, Last modification date: 2024-10-30)

Primary citation

Laursen, M.,Bublitz, M.,Moncoq, K.,Olesen, C.,Moeller, 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., 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 (2.5 Å)