1K8T Toxin,Lyase date Oct 25, 2001
title Crystal Structure Of The Adenylyl Cyclase Domain Of Anthrax Edema Factor (Ef)
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
Ec: 4.6.1.1
Engineered: Yes
 Organism_scientific: Bacillus Anthracis
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21
Expression_system_vector_type: Plasmid
symmetry Space Group: P 21 21 2
R_factor 0.229
crystal
cell
length a length b length c angle alpha angle beta angle gamma
50.476 203.604 74.034 90.00 90.00 90.00
method X-Ray Diffractionresolution 2.60 Å
ligand NI, SO4 enzyme Adenylate cyclase;. Adenylylcyclase;. Adenyl cyclase;. 3',5'-cyclic AMP synthetase. Lyase E.C.4.6.1.1 BRENDA
note 1K8T (Molecule of the Month:pdb28)is a representative structure
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 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.
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. 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.
Gene
Ontology
ChainFunctionProcessComponent
A
  • 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] (99 Kb) [Save to disk]
  • Biological Unit Coordinates (1k8t.pdb1.gz) 84 Kb
  • CSU: Contacts of Structural Units for 1K8T
  • Likely Quarternary Molecular Structure file(s) for 1K8T
  • Structure Factors (194 Kb)
  • Retrieve 1K8T in mmCIF format [Save to disk]
    • View 1K8T in 3D
  • On Jmol, a nice Rasmol like molecule viewer. This is good for easiest viewing of basic structure.
  • On FirstGlance, an excellent tool for a guided tour on the structure components, by E. Martz.
  • On AstexViewer, from MSD-EBI (viewer documentation).
  • On RasMol (Install RasMol freeware) Here's help on how to use RasMol.
    • Visual 3D analysis of 1K8T
  • Protein Explorer, Easier to use and more powerful than RasMol. (Win and Mac only)
  • Noncovalent Bond Finder displays the closest contacts to ligand or interface, reports distances, walks over water bridges.
  • STING, shows the sequence and maps the locations of sequence residues or residue ranges onto the 3D structure.
  • GRASS (Graphical Representation and Analysis of Structure Server)
  • Cartoon representation from PDB Cartoon
  • Ramachandran plot from PDBSum
    • Structure-derived information
  • Electron Density related parameters from EDS Electron Density Server, at Upsala
  • Dipole moment, from Dipole Server at Weizmann Institute
  • Crystal Contacts, from CryCo at Weizmann Institute
  • 3D motif for 1K8T, from MSDmotif at EBI
  • Classification of representative domains in scop (Structural Classification of Proteins)
        - Domain d1k8ta_, region A [Jmol] [rasmolscript] [script source]
  • Fold representative 1k8t from FSSP and Dali (Families of Structurally Similar Proteins)
    • Sequence-derived information
  • View one-letter amino acid or nucleotide sequence for each chain: [1k8t_A]
    • Other resources with information on 1K8T
  • InterPro: IPR003541 , IPR005165
  • PDBREPORT (protein verification by WHAT_CHECK procedures)
  • MMDB (Entrez's Structure Database)
    • Movements, Movies and Images
  • Images from IMB Jena Image Library of Biological Macromolecules.

    • You may enter another PDB ID code
    Go [Back], to the [PDB Lite page], to the [OCA Search page] or to the [PDB Home page]
    OCA© by Jaime Prilusky, 1996-2006
    Bioinformatics and Biological Computing
    Weizmann Institute of Science