1xfv
From Proteopedia
(New page: 200px<br /> <applet load="1xfv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xfv, resolution 3.35Å" /> '''Crystal structure o...) |
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| - | [[Image:1xfv.gif|left|200px]]<br /> | + | [[Image:1xfv.gif|left|200px]]<br /><applet load="1xfv" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xfv" size=" | + | |
caption="1xfv, resolution 3.35Å" /> | caption="1xfv, resolution 3.35Å" /> | ||
'''Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP'''<br /> | '''Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Edema factor (EF), a key anthrax exotoxin, has an anthrax protective | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1XFV 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 CA, MG and 3AT 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:// | + | 1XFV 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 <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=3AT:'>3AT</scene> 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1XFV OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Guo, Q.]] | [[Category: Guo, Q.]] | ||
[[Category: Shen, Q.]] | [[Category: Shen, Q.]] | ||
| - | [[Category: Tang, W | + | [[Category: Tang, W J.]] |
| - | [[Category: Zhukovskaya, N | + | [[Category: Zhukovskaya, N L.]] |
[[Category: 3AT]] | [[Category: 3AT]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: protein-protein interactions]] | [[Category: protein-protein interactions]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:21 2008'' |
Revision as of 13:54, 21 February 2008
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Crystal structure of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP
Contents |
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:[604214], Cerebral cavernous malformations-1 OMIM:[604214], Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations OMIM:[604214], Leukemia, acute T-cell lymphoblastic OMIM:[603025], Leukemia, acute myeloid OMIM:[603025]
About this Structure
1XFV is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens with , and 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
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