1YRU

Crystal Structure analysis of the adenylyl cyclaes catalytic domain of adenylyl cyclase toxin of Bordetella pertussis in presence of c-terminal calmodulin and 1mM calcium chloride

1YRU の概要

• エントリーDOI: 10.2210/pdb1yru/pdb
• 関連するPDBエントリー: 1YRT
• 分子名称: Bifunctional hemolysin-adenylate cyclase, Calmodulin, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: cyaa, cam, adenylyl cyclase, layse, toxin
• 由来する生物種: Bordetella pertussis; 詳細
• 細胞内の位置: Secreted: P15318; Cytoplasm, cytoskeleton, spindle: P62158
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48057.40

構造登録者

Guo, Q.,Shen, Y.,Tang, W.J. (登録日: 2005-02-04, 公開日: 2005-09-27, 最終更新日: 2024-02-14)

主引用文献

Guo, Q.,Shen, Y.,Lee, Y.S.,Gibbs, C.S.,Mrksich, M.,Tang, W.J.
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin
Embo J., 24:3190-3201, 2005

PubMed Abstract: CyaA is crucial for colonization by Bordetella pertussis, the etiologic agent of whooping cough. Here we report crystal structures of the adenylyl cyclase domain (ACD) of CyaA with the C-terminal domain of calmodulin. Four discrete regions of CyaA bind calcium-loaded calmodulin with a large buried contact surface. Of those, a tryptophan residue (W242) at an alpha-helix of CyaA makes extensive contacts with the calcium-induced, hydrophobic pocket of calmodulin. Mutagenic analyses show that all four regions of CyaA contribute to calmodulin binding and the calmodulin-induced conformational change of CyaA is crucial for catalytic activation. A crystal structure of CyaA-calmodulin with adefovir diphosphate, the metabolite of an approved antiviral drug, reveals the location of catalytic site of CyaA and how adefovir diphosphate tightly binds CyaA. The ACD of CyaA shares a similar structure and mechanism of activation with anthrax edema factor (EF). However, the interactions of CyaA with calmodulin completely diverge from those of EF. This provides molecular details of how two structurally homologous bacterial toxins evolved divergently to bind calmodulin, an evolutionarily conserved calcium sensor.

PubMed: 16138079
DOI: 10.1038/sj.emboj.7600800

実験手法

X-RAY DIFFRACTION (2.5 Å)