1xfx
Crystal structure of anthrax edema factor (EF) in complex with calmodulin in the presence of 10 millimolar exogenously added calcium chloride
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| , resolution 3.20Å | |||||||
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| Ligands: | , , | ||||||
| Gene: | cya (Bacillus anthracis) | ||||||
| Activity: | Adenylate cyclase, with EC number 4.6.1.1 | ||||||
| Related: | 1XFU, 1XFV, 1XFW, 1XFY, 1XFZ
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
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.
About this StructureAbout this Structure
1XFX is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Calcium-independent calmodulin binding and two-metal-ion catalytic mechanism of anthrax edema factor., Shen Y, Zhukovskaya NL, Guo Q, Florian J, Tang WJ, EMBO J. 2005 Mar 9;24(5):929-41. Epub 2005 Feb 17. PMID:15719022
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