1XFU

Crystal structure of anthrax edema factor (EF) truncation mutant, EF-delta 64 in complex with calmodulin

Summary for 1XFU

• Entry DOI: 10.2210/pdb1xfu/pdb
• Related: 1XFV 1XFW 1XFX 1XFY 1XFZ
• Descriptor: Calmodulin-sensitive adenylate cyclase, Calmodulin 2, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: protein-protein complex, lyase-metal binding protein complex, lyase/metal binding protein
• Biological source: Bacillus anthracis; More
• Cellular location: Secreted: P40136
• Total number of polymer chains: 12
• Total formula weight: 620543.10

Authors

Shen, Y.,Zhukovskaya, N.L.,Guo, Q.,Florian, J.,Tang, W.J. (deposition date: 2004-09-15, release date: 2005-05-03, Last modification date: 2024-02-14)

Primary citation

Shen, Y.,Zhukovskaya, N.L.,Guo, Q.,Florian, J.,Tang, W.J.
Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor.
EMBO J., 24:929-941, 2005

PubMed Abstract: Edema factor (EF), a key anthrax exotoxin, has an anthrax protective antigen-binding domain (PABD) and a calmodulin (CaM)-activated adenylyl cyclase domain. Here, we report the crystal structures of CaM-bound EF, revealing the architecture of EF PABD. CaM has N- and C-terminal domains and each domain can bind two calcium ions. Calcium binding induces the conformational change of CaM from closed to open. Structures of the EF-CaM complex show how EF locks the N-terminal domain of CaM into a closed conformation regardless of its calcium-loading state. This represents a mechanism of how CaM effector alters the calcium affinity of CaM and uncouples the conformational change of CaM from calcium loading. Furthermore, structures of EF-CaM complexed with nucleotides show that EF uses two-metal-ion catalysis, a prevalent mechanism in DNA and RNA polymerases. A histidine (H351) further facilitates the catalysis of EF by activating a water to deprotonate 3'OH of ATP. Mammalian adenylyl cyclases share no structural similarity with EF and they also use two-metal-ion catalysis, suggesting the catalytic mechanism-driven convergent evolution of two structurally diverse adenylyl cyclases.

PubMed: 15719022
DOI: 10.1038/sj.emboj.7600574

Experimental method

X-RAY DIFFRACTION (3.35 Å)