1S26

Structure of Anthrax Edema Factor-Calmodulin-alpha,beta-methyleneadenosine 5'-triphosphate Complex Reveals an Alternative Mode of ATP Binding to the Catalytic Site

Summary for 1S26

• Entry DOI: 10.2210/pdb1s26/pdb
• Related: 1K90 1LVC
• Descriptor: Calmodulin-sensitive adenylate cyclase, Calmodulin, YTTERBIUM (III) ION, ... (5 entities in total)
• Functional Keywords: ampcpp, edema factor, calmodulin, toxin, lyase-metal binding protein complex, lyase/metal binding protein
• Biological source: Bacillus anthracis; More
• Total number of polymer chains: 6
• Total formula weight: 228871.08

Authors

Shen, Y.,Zhukovskaya, N.L.,Bohm, A.,Tang, W.-J. (deposition date: 2004-01-08, release date: 2004-04-13, Last modification date: 2024-04-03)

Primary citation

Shen, Y.,Guo, Q.,Zhukovskaya, N.L.,Drum, C.L.,Bohm, A.,Tang, W.-J.
Structure of anthrax edema factor-calmodulin-adenosine-5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of ATP binding to the catalytic site
Biochem.Biophys.Res.Commun., 317:309-314, 2004

PubMed Abstract: Anthrax edema factor (EF) is a key virulence factor secreted by Bacillus anthracis. Here, we report a structure, at 3.0 A resolution, of the catalytic domain of EF (EF3) in complex with calmodulin (CaM) and adenosine 5'-(alpha,beta-methylene)-triphosphate (AMPCPP). Although the binding of the triphosphate of AMPCPP to EF3 can be superimposed on that of previously determined 3'deoxy-ATP (3'dATP) and 2'deoxy 3' anthraniloyl-ATP (2'd3' ANT-ATP) in EF3-CaM, the ribose and the adenine rings of AMPCPP are rotated approximately 105 and 180 degrees, respectively, relative to those of 3'dATP and 2'd3'ANT-ATP. Based on this model, K382 and F586 should play key roles in the recognition of adenine. However, mutations of these residues to alanine either separately or together cause only modest changes in Michaelis-Menten constants and IC50 values of AMPCPP and cAMP. Therefore, this alternate binding mode of the adenosine of AMPCPP binds to EF likely playing only a minor role in ATP binding and in catalysis.

PubMed: 15063758
DOI: 10.1016/j.bbrc.2004.03.046

Experimental method

X-RAY DIFFRACTION (3 Å)