1K93 Toxin,Lyase Metal Binding Protein date Oct 26, 2001
title Crystal Structure Of The Adenylyl Cyclase Domain Of Anthrax Edema Factor (Ef) In Complex With Calmodulin
authors C.L.Drum, S.-Z.Yan, J.Bard, Y.-Q.Shen, D.Lu, S.Soelaiman, Z.Grabarek, A.Bohm, W.-J.Tang
compound source
Molecule: Calmodulin-Sensitive Adenylate Cyclase
Chain: A, B, C
Ec: 4.6.1.1
Engineered: Yes
Organism_scientific: Bacillus Anthracis
Organism_common: Bacteria
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21
Expression_system_vector_type: Plasmid

Molecule: Calmodulin
Chain: D, E, F
Engineered: Yes

Organism_scientific: Homo Sapiens
Organism_common: Human
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21
Expression_system_vector_type: Plasmid
symmetry Space Group: I 2 2 2
R_factor 0.278
crystal
cell
length a length b length c angle alpha angle beta angle gamma
116.730 167.311 344.296 90.00 90.00 90.00
method X-Ray Diffractionresolution 2.95 Å
ligand CA, SO4 enzyme Adenylate cyclase;. Adenylylcyclase;. Adenyl cyclase;. 3',5'-cyclic AMP synthetase. Lyase E.C.4.6.1.1 BRENDA
note 1K93 (Molecule of the Month:pdb44)
domain The metal ion is coordinated by residues from ca; calmodulin probably binds in a multistep fashion first to residues in ca and then to residues present in the linker and the helical domain. The pa-binding region is found in both b.anthracis ef and lf. The c-terminal region contains the calmodulin-dependent activation domain and the catalytic site. This region is composed of three globular domains: ca, cb and a helical domain connected to ca by a linker. The n-terminal region contains the residues responsible for binding to pa63. The active site lies at the interface of ca and cb.
similarity Contains 4 ef-hand domains. Belongs to the adenylyl cyclase class-2 family.[Anthrax_toxA]
subunit Ef probably forms oligomers as part of the translocation machinery, formed by an heterocomplex of pa63 monomers and ef subunits, and it is functional as a monomer in the host cell. Anthrax toxins are composed of three distinct proteins, a protective antigen (pa), a lethal factor (lf) and an edema factor (ef). None of these is toxic by itself. Pa+lf forms the lethal toxin (letx); pa+ef forms the edema toxin (edtx).
catalytic activ. Atp = 3',5'-cyclic amp + diphosphate.
post-translat. modifications Ubiquitination results in a strongly decreased activity (by similarity). Phosphorylation results in a decreased activity (by similarity).
subcellular loc. Secreted protein.
enzyme regulation It has an absolute requirement for host calmodulin for its activation. Inhibited by ethyl 5- aminopyrazolo[1,5-a]quinazoline-3-carboxylate.
genes BXA0141, GBAA, cya (B. anthracis); cya (B. pertussis); GNAS (B. taurus); ADCY5 (C. familiaris); CAMC, CAMIII, CALM3 (H. sapiens); MT1302 (M. tuberculosis); Adcy2 (R. norvegicus); 4.1, 4.3, GRESAG (T. brucei); calm2 (X. laevis)
function One of the three proteins composing the anthrax toxin, the agent which infects many mammalian species and that may cause death. Among the enzymes to be stimulated by the calmodulin-ca(2+) complex are a number of protein kinases and phosphatases. 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. Calmodulin mediates the control of a large number of enzymes by ca(2+). Provokes dramatic elevation of intracellular camp levels in the host.
Gene
Ontology
ChainFunctionProcessComponent
A, C, B
  • nucleotide binding
  • magnesium ion binding
  • adenylate cyclase activity
  • calcium ion binding
  • protein binding
  • calmodulin binding
  • ATP binding
  • lyase activity
  • metal ion binding
  • cAMP biosynthetic process
  • pathogenesis
  • extracellular region
  • disease Calmodulin 3; Calm3
    Primary referenceStructural 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
    Data retrieval
  • Asymmetric unit, PDB entry: [header only] [complete with coordinates] (343 Kb) [Save to disk]
  • Biological Unit Coordinates (1k93.pdb1.gz) 105 Kb
  • Biological Unit Coordinates (1k93.pdb2.gz) 102 Kb
  • Biological Unit Coordinates (1k93.pdb3.gz) 108 Kb
  • CSU: Contacts of Structural Units for 1K93
  • Likely Quarternary Molecular Structure file(s) for 1K93
  • Structure Factors (618 Kb)
  • Retrieve 1K93 in mmCIF format [Save to disk]
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  • Classification of representative domains in scop (Structural Classification of Proteins)
        - Domain d1k93a_, region A [Jmol] [rasmolscript] [script source]
        - Domain d1k93b_, region B [Jmol] [rasmolscript] [script source]
        - Domain d1k93c_, region C [Jmol] [rasmolscript] [script source]
        - Domain d1k93d_, region D [Jmol] [rasmolscript] [script source]
        - Domain d1k93e_, region E [Jmol] [rasmolscript] [script source]
        - Domain d1k93f_, region F [Jmol] [rasmolscript] [script source]
  • Fold representative 1k93 from FSSP and Dali (Families of Structurally Similar Proteins)
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  • Sequence-derived information
  • View one-letter amino acid or nucleotide sequence for each chain: [1k93_D] [1k93_F] [1k93_B] [1k93_A] [1k93_E] [1k93_C]
  • Other resources with information on 1K93
  • InterPro: IPR003541 , IPR005165 , IPR001125 , IPR011992 , IPR002048
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