Pertussis toxin
Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium Bordetella pertussis.[1] PT is involved in the colonization of the respiratory tract and the establishment of infection. Research suggests PT may have a therapeutic role in treating a number of common human ailments including hypertension,[2] viral inhibition,[3] and autoimmune inhibition.[4]
Mechanism of pathogenesis
PT is an exotoxin with six subunits (named S1 through S5—each complex contains two copies of S4).[5] The subunits are arranged in a A-B structure: the A component is enzymatically active and is formed from the S1 subunit, while the B component is the receptor-binding portion and is made up of subunits S2–S5.[5] The subunits are encoded by ptx genes encoded on a large PT operon that also includes additional genes which encode Ptl proteins: Together these proteins form the PT secretion complex.[6]
PT is released from B. pertussis in an inactive form. When the B subunit binds to a cell membrane receptor, the A subunit (or protomer) becomes activated, perhaps through the action of glutathione and ATP.[7] PT catalyzes the ADP-ribosylation of the α subunits of the heterotrimeric G proteins Gi, Go, and Gt. This prevents the G proteins from interacting with G protein-coupled receptors on the cell membrane, thus interfering with intracellular communication.[8] Since the Gα subunits remain in their GDP-bound, inactive state, they are unable to inhibit adenylyl cyclase or open potassium channels.
References |
- ^ Ryan KJ; Ray CG (editors) (2004). Sherris Medical Microbiology, 4th ed., McGraw Hill. ISBN 0-8385-8529-9.
- ^ Kost C, Herzer W, Li P, Jackson E (1999). "Pertussis toxin-sensitive G-proteins and regulation of blood pressure in the spontaneously hypertensive rat". Clin Exp Pharmacol Physiol 26 (5-6): 449-55. PMID 10386237.
- ^ Alfano M, Pushkarsky T, Poli G, Bukrinsky M (2000). "The B-oligomer of pertussis toxin inhibits human immunodeficiency virus type 1 replication at multiple stages". J Virol 74 (18): 8767-70. PMID 10954581.
- ^ Bagley K, Abdelwahab S, Tuskan R, Fouts T, Lewis G (2002). "Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway". J Leukoc Biol 72 (5): 962-9. PMID 12429718.
- ^ a b Locht C, Antoine R (1995). "A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit". Biochimie 77 (5): 333-40. PMID 8527486.
- ^ Weiss A, Johnson F, Burns D (1993). "Molecular characterization of an operon required for pertussis toxin secretion". Proc Natl Acad Sci U S A 90 (7): 2970-4. PMID 8464913.
- ^ Finger H, von Koenig CHW (1996). Bordetella. In: Barron's Medical Microbiology (Barron S et al, eds.), 4th ed., Univ of Texas Medical Branch. (via NCBI Bookshelf) ISBN 0-9631172-1-1.
- ^ Burns D (1988). "Subunit structure and enzymic activity of pertussis toxin". Microbiol Sci 5 (9): 285-7. PMID 2908558.
| Transferases: glycosyltransferases (EC 2.4) |
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2.4.1 - Hexosyltransferases:
glucosyltransferase | Phosphorylase (Starch, Glycogen, Myo-) - Glycogen synthase - Debranching enzyme - Branching enzyme - 1,3-beta-glucan synthase - Ceramide glucosyltransferase |
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2.4.1 - Hexosyltransferases:
other | Galactosyltransferase (Lactose synthase, B-N-acetylglucosaminyl-glycopeptide b-1,4-galactosyltransferase) - Glucuronosyltransferase (UGT1A1, UGT2B7, Hyaluronan synthase) - Fucosyltransferase (POFUT1, POFUT2) |
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2.4.2 - Pentosyltransferases:
ADP ribose | Cholera toxin - Diphtheria toxin - Pertussis toxin - Poly ADP ribose polymerase |
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2.4.2 - Pentosyltransferases:
other | Purine nucleoside phosphorylase - Adenine phosphoribosyltransferase - Hypoxanthine-guanine phosphoribosyltransferase - Uracil phosphoribosyltransferase - Amidophosphoribosyltransferase |
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