1k90: Difference between revisions
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==Overview== | ==Overview== | ||
Oedema factor, a calmodulin-activated adenylyl cyclase, is important in | Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets. | ||
==Disease== | ==Disease== | ||
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[[Category: Bard, J.]] | [[Category: Bard, J.]] | ||
[[Category: Bohm, A.]] | [[Category: Bohm, A.]] | ||
[[Category: Drum, C | [[Category: Drum, C L.]] | ||
[[Category: Grabarek, Z.]] | [[Category: Grabarek, Z.]] | ||
[[Category: Lu, D.]] | [[Category: Lu, D.]] | ||
[[Category: Shen, Y | [[Category: Shen, Y Q.]] | ||
[[Category: Soelaiman, S.]] | [[Category: Soelaiman, S.]] | ||
[[Category: Tang, W | [[Category: Tang, W J.]] | ||
[[Category: Yan, S | [[Category: Yan, S Z.]] | ||
[[Category: 3AT]] | [[Category: 3AT]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: oedema factor adenylyl cyclase anthrax calmodulin]] | [[Category: oedema factor adenylyl cyclase anthrax calmodulin]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:31:25 2008'' | ||
Revision as of 14:31, 21 February 2008
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Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF) in complex with calmodulin and 3' deoxy-ATP
OverviewOverview
Oedema factor, a calmodulin-activated adenylyl cyclase, is important in the pathogenesis of anthrax. Here we report the X-ray structures of oedema factor with and without bound calmodulin. Oedema factor shares no significant structural homology with mammalian adenylyl cyclases or other proteins. In the active site, 3'-deoxy-ATP and a single metal ion are well positioned for catalysis with histidine 351 as the catalytic base. This mechanism differs from the mechanism of two-metal-ion catalysis proposed for mammalian adenylyl cyclases. Four discrete regions of oedema factor form a surface that recognizes an extended conformation of calmodulin, which is very different from the collapsed conformation observed in other structures of calmodulin bound to effector peptides. On calmodulin binding, an oedema factor helical domain of relative molecular mass 15,000 undergoes a 15 A translation and a 30 degrees rotation away from the oedema factor catalytic core, which stabilizes a disordered loop and leads to enzyme activation. These allosteric changes provide the first molecular details of how calmodulin modulates one of its targets.
DiseaseDisease
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 StructureAbout this Structure
1K90 is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens with , and as ligands. The following page contains interesting information on the relation of 1K90 with [Anthrax Toxin]. Active as Adenylate cyclase, with EC number 4.6.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for the activation of anthrax adenylyl cyclase exotoxin by calmodulin., Drum CL, Yan SZ, Bard J, Shen YQ, Lu D, Soelaiman S, Grabarek Z, Bohm A, Tang WJ, Nature. 2002 Jan 24;415(6870):396-402. PMID:11807546
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