| 1S5E |
Transerase,Toxin |
date |
Jan 20, 2004  |
|---|
| title | Cholera Holotoxin, Crystal Form 1 |
| authors | C.J.O'Neal, E.I.Amaya, M.G.Jobling, R.K.Holmes, W.G.Hol |
| compound |
source |
Molecule: Cholera Enterotoxin, A Chain Precursor
Chain: A, B
Synonym: Nad(+)--Diphthamide Adp- Ribosyltransferase, Cholera Enterotoxin A Subunit;
Ec: 2.4.2.36
Engineered: Yes
|
Organism_scientific: Vibrio Cholerae
Organism_common: Bacteria
Gene: Ctxa, Toxa, Vc1457
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21(De3)
Expression_system_vector_type: Plasmid
Expression_system_plasmid: Parct5
|
Molecule: Cholera Toxin B Protein (Ctb)
Chain: D, E, F, G, H, J, K, L, M, N
Engineered: Yes
|
Organism_scientific: Vibrio Cholerae
Organism_common: Bacteria
Gene: Ctxb, Toxb, Vc1456
Expression_system: Escherichia Coli
Expression_system_common: Bacteria
Expression_system_strain: Bl21(De3)
Expression_system_vector_type: Plasmid
Expression_system_plasmid: Parct5
|
| symmetry | Space Group: P 1 21 1
| R_factor | 0.167 |
crystal
cell |
| length a |
length b |
length c |
angle alpha |
angle beta |
angle gamma |
| 59.931 |
108.230 |
122.976 |
90.00 |
95.89 |
90.00 |
|
| method | X-Ray Diffraction | resolution | 1.90 Å |
| ligand | GAL, NA
| enzyme | NAD+-diphthamide ADP-ribosyltransferase;. ADP-ribosyltransferase;. Mono(ADPribosyl)transferase;. NAD-diphthamide ADP-ribosyltransferase. Transferase
E.C.2.4.2.36
BRENDA
|
| domain | The four c-terminal residues of the a2 chain occupy the central pore of the holotoxin. Deletion of this residues weakens the interaction between the a subunit and the b pentamer whithout impairing the pentamer formation. |
| similarity | Belongs to the Enterotoxin_b family. |
| subunit | The a subunit contains two chains, a1 and a2, linked by a disulfide bridge. The holotoxin (choleragen) consists of a pentameric ring of b subunits whose central pore is occupied by the a subunit. |
| catalytic activ. | Nad(+) + peptide diphthamide = nicotinamide + peptide n-(adp-d-ribosyl)diphthamide. |
| genes | HEGFL, HBEGF (H. sapiens); ctxA, ctxB (V. cholerae); EFT2 (S. cerevisiae) |
| function | This leads to an overproduction of camp and eventually to a hypersecretion of chloride and bicarbonate followed by water, resulting in the characteristic cholera stool. The a2 chain tethers a1 to the pentameric ring. The a1 chain catalyzes the adp-ribosylation of gs alpha, a gtp-binding regulatory protein, to activate the adenylate cyclase. It can bind five gm1 gangliosides. The b subunit pentameric ring directs the a subunit to its target by binding to the gm1 gangliosides present on the surface of the intestinal epithelial cells. It has no toxic activity by itself. |
Gene
Ontology |
| Chain | Function | Process | Component | | A, B | catalytic activitytransferase activitytransferase activity, transf...NAD+-diphthamide ADP-ribosyl... | pathogenesis | extracellular region |
| F, J, N, K, E, H, M, D, G, L |
| pathogenesis | extracellular regionmembrane |
|
| disease | Diphtheria,susceptibility to
|
| Primary reference | Crystal Structures of an Intrinsically Active Cholera Toxin Mutant Yield Insight into the Toxin Activation Mechanism(,)., O'Neal CJ, Amaya EI, Jobling MG, Holmes RK, Hol WG, Biochemistry 2004 Apr 6;43(13):3772-3782. PMID:15049684 |
