2OA0

Crystal structure of Calcium ATPase with bound ADP and cyclopiazonic acid

Summary for 2OA0

• Entry DOI: 10.2210/pdb2oa0/pdb
• Related: 2O9J
• 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, ... (4 entities in total)
• Functional Keywords: calcium atpase, serca, mycotoxin, cyclopiazonic acid, 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: 110390.47

Authors

Young, H.S.,Moncoq, K.A. (deposition date: 2006-12-14, release date: 2007-02-06, Last modification date: 2023-08-30)

Primary citation

Moncoq, K.,Trieber, C.A.,Young, H.S.
The molecular basis for cyclopiazonic Acid inhibition of the sarcoplasmic reticulum calcium pump.
J.Biol.Chem., 282:9748-9757, 2007

PubMed Abstract: The sarcoplasmic reticulum Ca(2+)-ATPase is essential for calcium reuptake in the muscle contraction-relaxation cycle. Here we present structures of a calcium-free state with bound cyclopiazonic acid (CPA) and magnesium fluoride at 2.65 A resolution and a calcium-free state with bound CPA and ADP at 3.4A resolution. In both structures, CPA occupies the calcium access channel delimited by transmembrane segments M1-M4. Inhibition of Ca(2+)-ATPase is stabilized by a polar pocket that surrounds the tetramic acid of CPA and a hydrophobic platform that cradles the inhibitor. The calcium pump residues involved include Gln(56), Leu(61), Val(62), and Asn(101). We conclude that CPA inhibits the calcium pump by blocking the calcium access channel and immobilizing a subset of transmembrane helices. In the E2(CPA) structure, ADP is bound in a distinct orientation within the nucleotide binding pocket. The adenine ring is sandwiched between Arg(489) of the nucleotide-binding domain and Arg(678) of the phosphorylation domain. This mode of binding conforms to an adenine recognition motif commonly found in ATP-dependent proteins.

PubMed: 17259168
DOI: 10.1074/jbc.M611653200

Experimental method

X-RAY DIFFRACTION (3.4 Å)