1LVC

Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 2' deoxy, 3' anthraniloyl ATP

Summary for 1LVC

• Entry DOI: 10.2210/pdb1lvc/pdb
• Related: 1K90
• Descriptor: calmodulin-sensitive adenylate cyclase, calmodulin, YTTERBIUM (III) ION, ... (5 entities in total)
• Functional Keywords: helical domain, protein-protein complex, lyase
• Biological source: Bacillus anthracis; More
• Total number of polymer chains: 6
• Total formula weight: 228969.64

Authors

Shen, Y.,Lee, Y.-S.,Soelaiman, S.,Bergson, P.,Lu, D.,Chen, A.,Beckingham, K.,Grabarek, Z.,Mrksich, M.,Tang, W.-J. (deposition date: 2002-05-28, release date: 2002-12-04, Last modification date: 2024-02-14)

Primary citation

Shen, Y.,Lee, Y.-S.,Soelaiman, S.,Bergson, P.,Lu, D.,Chen, A.,Beckingham, K.,Grabarek, Z.,Mrksich, M.,Tang, W.-J.
Physiological calcium concentrations regulate calmodulin binding and catalysis of adenylyl cyclase exotoxins
Embo J., 21:6721-6732, 2002

PubMed Abstract: Edema factor (EF) and CyaA are calmodulin (CaM)-activated adenylyl cyclase exotoxins involved in the pathogenesis of anthrax and whooping cough, respectively. Using spectroscopic, enzyme kinetic and surface plasmon resonance spectroscopy analyses, we show that low Ca(2+) concentrations increase the affinity of CaM for EF and CyaA causing their activation, but higher Ca(2+) concentrations directly inhibit catalysis. Both events occur in a physiologically relevant range of Ca(2+) concentrations. Despite the similarity in Ca(2+) sensitivity, EF and CyaA have substantial differences in CaM binding and activation. CyaA has 100-fold higher affinity for CaM than EF. CaM has N- and C-terminal globular domains, each binding two Ca(2+) ions. CyaA can be fully activated by CaM mutants with one defective C-terminal Ca(2+)-binding site or by either terminal domain of CaM while EF cannot. EF consists of a catalytic core and a helical domain, and both are required for CaM activation of EF. Mutations that decrease the interaction of the helical domain with the catalytic core create an enzyme with higher sensitivity to Ca(2+)-CaM activation. However, CyaA is fully activated by CaM without the domain corresponding to the helical domain of EF.

PubMed: 12485993
DOI: 10.1093/emboj/cdf681

Experimental method

X-RAY DIFFRACTION (3.6 Å)