Literature summary for 4.6.1.1 extracted from

Cheung, G.Y.; Kelly, S.M.; Jess, T.J.; Prior, S.; Price, N.C.; Parton, R.; Coote, J.G.
Functional and structural studies on different forms of the adenylate cyclase toxin of Bordetella pertussis (2009), Microb. Pathog., 46, 36-42.

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Cloned(Commentary)

Cloned (Comment)	Organism
expression of different recombinant forms of adenylate cyclase toxin, insertion mutant CyaA, fully functional CyaA, CyaA* lacking adenylate cyclase enzymatic activity CyaA, and non-acylated forms of the two latter toxins, proCyaA and proCyaA	Bordetella pertussis

Protein Variants

Protein Variants	Comment	Organism
additional information	the CyaA mutant with a Cys/Thr insertion at amino acids 188/189 is unable to kill J774 mouse macrophage-like cells at a concentration as high as 0.010 mg/ml, yet lytic activity towards erythrocytes is retained. Binding of a monoclonal antibody distal to the inactivated catalytic site restored cytotoxicity towards J774 cells and further enhances haemolytic activity, construction of mutant CyaA* lacking adenylate cyclase enzymatic activity, and of non-acylated forms of wild-type CyaA and mutant CyaA, proCyaA and proCyaA, CyaA* is as cytotoxic towards J774.2 cells as CyaA and mediates cell killing at a faster rate than CyaA at higher concentration than 0.0001 mg/ml. Non-acylated mutant proCyaA* has no detectable cytotoxic or apoptotic activity. A 500fold higher concentration of non-acylated or mutant CyaA is necessary for inhibition of the zymosan-stimulated oxidative burst	Bordetella pertussis

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
extracellular	CyaA is secreted	Bordetella pertussis	-	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	CyaA is a calcium-binding protein, Ca2+ binding leads a a rearrangement of the enzyme's secondary structure, overview	Bordetella pertussis

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
177000	-	CyaA	Bordetella pertussis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP	Bordetella pertussis	interaction with and invasion of mammalian target cells, such as monocytes and neutrophils, that express the CD11b/CD18, CR3, receptor, is facilitated by acylation of CyaA. CyaA forms small, transient, ionpermeable channels in target membranes. CyaA-induced haemolysis requires higher toxin concentrations and occurs more slowly than intoxication	3',5'-cyclic-AMP + diphosphate	-	?
additional information	Bordetella pertussis	at high toxin concentrations, non-acylated CyaA can intoxicate macrophages by delivery of the catalytic domain. CyaA, but not mutant CyaA*, is able to induce caspase 3/7 activity, CyaA causes 50% inhibition of the zymosan-stimulated oxidative burst	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Bordetella pertussis	P0DKX7	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	CyaA is synthesized as a protoxin proCyaA that is post-translationally acylated by a separate protein, CyaC, non-acylated wild-typeroCyaA has no detectable cytotoxic or apoptotic activity	Bordetella pertussis

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP	-	Bordetella pertussis	3',5'-cyclic-AMP + diphosphate	-	?
ATP	interaction with and invasion of mammalian target cells, such as monocytes and neutrophils, that express the CD11b/CD18, CR3, receptor, is facilitated by acylation of CyaA. CyaA forms small, transient, ionpermeable channels in target membranes. CyaA-induced haemolysis requires higher toxin concentrations and occurs more slowly than intoxication	Bordetella pertussis	3',5'-cyclic-AMP + diphosphate	-	?
additional information	at high toxin concentrations, non-acylated CyaA can intoxicate macrophages by delivery of the catalytic domain. CyaA, but not mutant CyaA*, is able to induce caspase 3/7 activity, CyaA causes 50% inhibition of the zymosan-stimulated oxidative burst	Bordetella pertussis	?	-	?

Subunits

Subunits	Comment	Organism
More	CyaA has two functional domains: the C-terminal domain of about 1300 amino acids, which has membrane-targeting and pore-forming activity, and the 400 amino acid N-terminal domain which has adenylate cyclase enzymatic activity. Intoxication can be triggered by CyaA monomers at low toxin concentrations, whereas cytolytic activity is a co-operative event, mediated by an oligomeric structure consisting of two or more toxin monomers responsible for the production of the pores or channels at higher toxin concentrations	Bordetella pertussis

Synonyms

Synonyms	Comment	Organism
adenylate cyclase toxin	-	Bordetella pertussis
CyaA	-	Bordetella pertussis
More	CyaA belongs to the repeats in toxin, RTX, family	Bordetella pertussis

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Release 2023.1 (January 2023)