1y0v
From Proteopedia
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Crystal structure of anthrax edema factor (EF) in complex with calmodulin and pyrophosphate
Overview
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 Structure
1Y0V is a Protein complex structure of sequences from Bacillus anthracis and Xenopus laevis with MG, CA and POP as ligands. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Wed Nov 21 06:28:51 2007
