View source for 1xfx

[[Image:1xfx.gif|left|200px]]<br />
<applet load="1xfx" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="1xfx, resolution 3.20&Aring;" />
'''Crystal structure of anthrax edema factor (EF) in complex with calmodulin in the presence of 10 millimolar exogenously added calcium chloride'''<br />

==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.

==Disease==
Known diseases associated with this structure: Cavernous malformations of CNS and retina OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Cerebral cavernous malformations-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604214 604214]], Leukemia, acute T-cell lymphoblastic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603025 603025]]

==About this Structure==
1XFX is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Adenylate_cyclase Adenylate cyclase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.1 4.6.1.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1XFX 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15719022 15719022]
[[Category: Adenylate cyclase]]
[[Category: Bacillus anthracis]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Florian, J.]]
[[Category: Guo, Q.]]
[[Category: Shen, Y.]]
[[Category: Tang, W.J.]]
[[Category: Zhukovskaya, N.L.]]
[[Category: CA]]
[[Category: MG]]
[[Category: protein-protein interaction]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:04:53 2007''