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|1yrt, resolution 2.10Å ()|
|Gene:||cya, cyaA (Bordetella pertussis), CALM1, CALM2, CALM3 (Homo sapiens)|
Crystal Structure analysis of the adenylyl cyclaes catalytic domain of adenylyl cyclase toxin of Bordetella pertussis in presence of c-terminal calmodulin
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.
Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin., Guo Q, Shen Y, Lee YS, Gibbs CS, Mrksich M, Tang WJ, EMBO J. 2005 Sep 21;24(18):3190-201. Epub 2005 Sep 1. PMID:16138079
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Guo Q, Shen Y, Lee YS, Gibbs CS, Mrksich M, Tang WJ. Structural basis for the interaction of Bordetella pertussis adenylyl cyclase toxin with calmodulin. EMBO J. 2005 Sep 21;24(18):3190-201. Epub 2005 Sep 1. PMID:16138079