1K93

Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin

1K93 の概要

• エントリーDOI: 10.2210/pdb1k93/pdb
• 関連するPDBエントリー: 1K8T 1K9O
• 分子名称: CALMODULIN-SENSITIVE ADENYLATE CYCLASE, CALMODULIN, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: edema factor, calmodulin, adenylyl cyclase, anthrax, toxin, lyase-metal binding protein complex, lyase/metal binding protein
• 由来する生物種: Bacillus anthracis; 詳細
• 細胞内の位置: Secreted: P40136; Cytoplasm, cytoskeleton, spindle: P02593
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 225746.09

構造登録者

Drum, C.L.,Yan, S.-Z.,Bard, J.,Shen, Y.-Q.,Lu, D.,Soelaiman, S.,Grabarek, Z.,Bohm, A.,Tang, W.-J. (登録日: 2001-10-26, 公開日: 2002-01-23, 最終更新日: 2024-04-03)

主引用文献

Drum, C.L.,Yan, S.-Z.,Bard, J.,Shen, Y.-Q.,Lu, D.,Soelaiman, S.,Grabarek, Z.,Bohm, A.,Tang, W.-J.
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin.
Nature, 415:396-402, 2002

PubMed Abstract: Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.

PubMed: 11807546
DOI: 10.1038/415396a

実験手法

X-RAY DIFFRACTION (2.95 Å)