| 1PK0 |
Lyase Metal Binding Protein |
date |
Jun 04, 2003  |
|---|
| title | Crystal Structure Of The Ef3-Cam Complexed With Pmeapp |
| authors | Y.Shen, W.J.Tang |
| compound |
source |
Molecule: Calmodulin-Sensitive Adenylate Cyclase
Chain: A, B, C
Fragment: Residues 292-798
Synonym: Atp Pyrophosphate-Lyase, Adenylyl Cyclase, Edema Factor, Ef, Anthrax Edema Toxin Adenylate Cyclase Component;
Ec: 4.6.1.1
Engineered: Yes
|
Organism_scientific: Bacillus Anthracis
Gene: Cya Or Pxo1-122
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_vector_type: Plasmid
Expression_system_plasmid: Pproex
|
Molecule: Calmodulin
Chain: D, E, F
Engineered: Yes
|
Organism_scientific: Homo Sapiens
Organism_common: Human
Gene: (Calm1 Or Cam1 Or Calm Or Cam)
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21(De3)
Expression_system_vector_type: Plasmid
Expression_system_plasmid: Pproex
|
| symmetry | Space Group: I 2 2 2
| R_factor | 0.264 |
crystal
cell |
| length a |
length b |
length c |
angle alpha |
angle beta |
angle gamma |
| 116.263 |
165.759 |
342.409 |
90.00 |
90.00 |
90.00 |
|
| method | X-Ray Diffraction | resolution | 3.30 Å |
| ligand | CA, EMA, YB
| enzyme | Adenylate cyclase;. Adenylylcyclase;. Adenyl cyclase;. 3',5'-cyclic AMP synthetase. Lyase
E.C.4.6.1.1
BRENDA
|
| 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 | |
| disease | Calmodulin 3; Calm3
|
| Primary reference | Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection., Shen Y, Zhukovskaya NL, Zimmer MI, Soelaiman S, Bergson P, Wang CR, Gibbs CS, Tang WJ, Proc Natl Acad Sci U S A 2004 Mar 2;101(9):3242-7. Epub 2004 Feb 20. PMID:14978283 |
