1k8t

Crystal structure of the adenylyl cyclase domain of anthrax edema factor (EF)

spinqualitylabelsall models 1k8t, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1k8t is a 1 chain structure with sequence from "bacillus_cereus_var._anthracis"_(cohn_1872)_smith_et_al._1946 "bacillus cereus var. anthracis" (cohn 1872) smith et al. 1946. The April 2002 RCSB PDB Molecule of the Month feature on Anthrax Toxin by David S. Goodsell is 10.2210/rcsb_pdb/mom_2002_4. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NI, SO4 Activity: Adenylate cyclase, with EC number 4.6.1.1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CYAA_BACAN] One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. EF is a calmodulin-dependent adenylyl cyclase that, when associated with PA, causes edema. EF is not toxic by itself and it is required for the survival of germinated spores within macrophages at the early stages of infection. Provokes dramatic elevation of intracellular cAMP levels in the host. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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