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

Summary for 1YRU

• Entry DOI: 10.2210/pdb1yru/pdb
• Related: 1YRT
• Descriptor: Bifunctional hemolysin-adenylate cyclase, Calmodulin, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: cyaa, cam, adenylyl cyclase, layse, toxin
• Biological source: Bordetella pertussis; More
• Cellular location: Secreted: P15318; Cytoplasm, cytoskeleton, spindle: P62158
• Total number of polymer chains: 2
• Total formula weight: 48057.40

Authors

Guo, Q.,Shen, Y.,Tang, W.J. (deposition date: 2005-02-04, release date: 2005-09-27, Last modification date: 2024-02-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)