2OA0

Crystal structure of Calcium ATPase with bound ADP and cyclopiazonic acid

2OA0 の概要

• エントリーDOI: 10.2210/pdb2oa0/pdb
• 関連するPDBエントリー: 2O9J
• 分子名称: 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)
• 機能のキーワード: calcium atpase, serca, mycotoxin, cyclopiazonic acid, hydrolase
• 由来する生物種: Oryctolagus cuniculus (rabbit)
• 細胞内の位置: Endoplasmic reticulum membrane ; Multi-pass membrane protein : P04191
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110390.47

構造登録者

Young, H.S.,Moncoq, K.A. (登録日: 2006-12-14, 公開日: 2007-02-06, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (3.4 Å)