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Literature summary for 4.6.1.1 extracted from
- Class III adenylyl cyclases: molecular mechanisms of catalysis and regulation (2006), Cell. Mol. Life Sci., 63, 1736-1751.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| bicarbonate | activates CyaB1 2.5fold | Nostoc sp. PCC 7120 = FACHB-418 |  |
| bicarbonate | stimulates 2.5fold | Arthrospira platensis | |
| Calmodulin | - |
Rattus norvegicus | |
| CAP | for full activation of the AC in vivo RAS2-GTP, CAP and Gpa2 modulate the enzyme synergistically | Schizosaccharomyces pombe | |
| Gpa2 | for full activation of the AC in vivo RAS2-GTP, CAP and Gpa2 modulate the enzyme synergistically | Schizosaccharomyces pombe | |
| additional information | 2-4fold enhancement of adenylate cyclase activity by the histidine kinase-receiver system, histidine kinase domain autophosphorylates on His572, subsequently the phosphate is transferred to the second receiver domain Asp895, which is adjacent to the CHD domain | Arthrospira platensis | |
| additional information | blue-light irradiation activates the AC 80fold | Euglena gracilis | |
| additional information | cytosolic regulator of AC essential for activation of ACA, ACG is activated by high osmolarity | Dictyostelium discoideum | |
| additional information | GAF domains bind cAMP and thereby increase the adenylate cyclase activity 27fold, thus functioning as an autoactivating switch and creating a feed-forward stimulatory mechanism | Nostoc sp. PCC 7120 = FACHB-418 | |
| additional information | Ras-GTP and mediates activation of the AC | Ustilago maydis | |
| additional information | two signals activate the single, class IIId AC in vivo, a shift from carbohydrate-free to glucose-containing medium and an intracellular acidification upon carbon starvation | Saccharomyces cerevisiae | |
| Ras2 | for full activation of the AC in vivo RAS2-GTP, CAP and Gpa2 modulate the enzyme synergistically | Schizosaccharomyces pombe | |
| Ras2 | in its GTP-bound form is essential for activation in vivo and functions as a direct stimulator of adenylate cyclase activity in vitro | Saccharomyces cerevisiae |
Application
| Application | Comment | Organism |
|---|---|---|
| additional information | 15 putative AC genes present | Mycobacterium tuberculosis |
| additional information | ACA has the same architecture as mammalian membrane-bound ACs, is essential for reacting to and production of cAMP. ACG is essential for germination. ACB is required for terminal maturation of spores | Dictyostelium discoideum |
| additional information | CyaB1 is composed of two GAF domains, a PAS domain, a CHD and a single tetratricopeptide repeat | Nostoc sp. PCC 7120 = FACHB-418 |
| additional information | CyaB2 is composed of two GAF domains, a PAS domain, a CHD and a single tetratricopeptide repeat | Nostoc sp. PCC 7120 = FACHB-418 |
| additional information | CyaC consists of a receiver domain, two GAF domains, a histidine kinase domain, another receiver and a CHD | Nostoc sp. PCC 7120 = FACHB-418 |
| additional information | involved in sensing high osmotic pressure | Myxococcus xanthus |
| additional information | senses ional changes in the environment | Chlamydomonas reinhardtii |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
- |
Rattus norvegicus |
- |
Saccharomyces cerevisiae |
- |
Dictyostelium discoideum |
| expression in Escherichia coli | Mycobacterium tuberculosis |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
- |
Trypanosoma brucei |
- |
Arthrospira platensis |
| crystal structure of the tandem GAF domains of CyaB2 shows an antiparallel dimer, in which GAFA of one monomer binds to GAFB of the other and vice versa | Nostoc sp. PCC 7120 = FACHB-418 |
| crystal structures of Rv1264 holoenzyme in the active and inhibited states, N-terminal domain is alpha-helical and forms a tight platform-like dimer. In the crystal structure of the Rv1900c CHD the residue is not in contact with the ribose moiety of the ATP-analogue alpha,beta-methylene-ATP | Mycobacterium tuberculosis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | deletion of CyaC reduces cellular cAMP levels to 25% of wild-type, in the mutant cells cAMP levels are not lowered by light as in wild-type cells, but stay constant | Nostoc sp. PCC 7120 = FACHB-418 |
| additional information | disruption of a class IIIb AC gene results in strong attenuation | Pseudomonas aeruginosa |
| additional information | knockout of sAC in mice causes male sterility by impaired sperm motility, while spermatogenesis is not affected | Mus musculus |
| additional information | mutation of either His572 or Asp895 greatly reduces AC activity | Arthrospira platensis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | full-length enzyme contains a large autoinhibitory C-terminal | Rattus norvegicus |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0005 | - |
ATP | - |
Euglena gracilis | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | in Rv3645 a membrane anchor consisting of 6 putative transmembrane helices is linked to a class IIIb CHD via a HAMP domain, the membrane anchor of Rv3645 may serve as a sensor | Mycobacterium tuberculosis | 16020 | - |
| membrane | the N-terminal half of the class IIIb AC consists of a predicted membrane-associated sensor domain | Pseudomonas aeruginosa | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ca2+ | - |
Rattus norvegicus | |
| Ca2+ | activates | Arthrospira platensis | |
| Mg2+ | 3' hydroxyl group bound to a Mg-ion complexed to RP-ATP-alphaS | Arthrospira platensis | |
Molecular Weight [Da]
| Molecular Weight [Da] | Molecular Weight Maximum [Da] | Comment | Organism |
|---|---|---|---|
| 11200 | - |
alpha-subunit | Euglena gracilis |
| 48000 | - |
splicing variant | Rattus norvegicus |
| 94000 | - |
beta-subunit | Euglena gracilis |
| 187000 | - |
full-length enzyme | Rattus norvegicus |
| 400000 | - |
- |
Euglena gracilis |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Arthrospira platensis | - |
- |
- |
| Bacillus anthracis | - |
- |
- |
| Bordetella pertussis | - |
- |
- |
| Caenorhabditis elegans | - |
- |
- |
| Chlamydomonas reinhardtii | - |
- |
- |
| Chloroflexus aurantiacus | - |
- |
- |
| Dictyostelium discoideum | - |
- |
- |
| Drosophila melanogaster | - |
- |
- |
| Escherichia coli | - |
- |
- |
| Euglena gracilis | - |
- |
- |
| Mus musculus | - |
- |
- |
| Mycobacterium tuberculosis | P9WQ35 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WQ35 | - |
- |
| Myxococcus xanthus | - |
- |
- |
| Nostoc sp. PCC 7120 = FACHB-418 | Q7A2D9 | - |
- |
| Nostoc sp. PCC 7120 = FACHB-418 | Q8YMH0 | - |
- |
| Nostoc sp. PCC 7120 = FACHB-418 | Q8YVS0 | - |
- |
| Pseudomonas aeruginosa | - |
- |
- |
| Rattus norvegicus | - |
- |
- |
| Saccharomyces cerevisiae | - |
- |
- |
| Schizosaccharomyces pombe | - |
- |
- |
| Sinorhizobium meliloti | - |
- |
- |
| Trypanosoma brucei | - |
- |
- |
| Ustilago maydis | - |
- |
- |
| Yersinia enterocolitica | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Rattus norvegicus |
- |
Arthrospira platensis |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | - |
Rattus norvegicus | - |
| sperm | - |
Mus musculus | - |
| spore | ACB is expressed during late development | Dictyostelium discoideum | - |
| testis | - |
Rattus norvegicus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP | - |
Arthrospira platensis | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | - |
Yersinia enterocolitica | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | - |
Mycobacterium tuberculosis | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | - |
Nostoc sp. PCC 7120 = FACHB-418 | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | ACA, cAMP signalling is essential for aggregation and development of the amoebae upon starvation | Dictyostelium discoideum | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | cAMP is required for expression of the secretion system by which virulence factors are translocated to the host cell | Pseudomonas aeruginosa | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | in CyaB1 only GAFB binds cAMP | Nostoc sp. PCC 7120 = FACHB-418 | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | in CyaB2 both GAFA and GAFB are cAMP receptors | Nostoc sp. PCC 7120 = FACHB-418 | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | photoavoidance is triggered by cAMP formed by a blue-light activated class IIIb AC | Euglena gracilis | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | - |
Mycobacterium tuberculosis H37Rv | 3',5'-cAMP + diphosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| heterodimer | enzymes ACB and ACG | Dictyostelium discoideum |
| heterotetramer | - |
Euglena gracilis |
| homodimer | - |
Saccharomyces cerevisiae |
| homodimer | - |
Pseudomonas aeruginosa |
| homodimer | - |
Trypanosoma brucei |
| homodimer | - |
Myxococcus xanthus |
| homodimer | - |
Arthrospira platensis |
| homodimer | - |
Mycobacterium tuberculosis |
| homodimer | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| homodimer | enzyme ACA | Dictyostelium discoideum |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ACA | - |
Dictyostelium discoideum |
| ACB | - |
Dictyostelium discoideum |
| ACG | - |
Dictyostelium discoideum |
| class I AC | - |
Escherichia coli |
| class I AC | - |
Yersinia enterocolitica |
| class II AC | - |
Pseudomonas aeruginosa |
| class II AC | - |
Bordetella pertussis |
| class II AC | - |
Bacillus anthracis |
| class III AC | - |
Drosophila melanogaster |
| class III AC | - |
Sinorhizobium meliloti |
| class III AC | - |
Chlamydomonas reinhardtii |
| class III AC | - |
Mus musculus |
| class III AC | - |
Rattus norvegicus |
| class III AC | - |
Saccharomyces cerevisiae |
| class III AC | - |
Trypanosoma brucei |
| class III AC | - |
Dictyostelium discoideum |
| class III AC | - |
Schizosaccharomyces pombe |
| class III AC | - |
Caenorhabditis elegans |
| class III AC | - |
Myxococcus xanthus |
| class III AC | - |
Arthrospira platensis |
| class III AC | - |
Ustilago maydis |
| class III AC | - |
Chloroflexus aurantiacus |
| class III AC | - |
Mycobacterium tuberculosis |
| class III AC | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| class III adenylyl cyclase | - |
Drosophila melanogaster |
| class III adenylyl cyclase | - |
Sinorhizobium meliloti |
| class III adenylyl cyclase | - |
Chlamydomonas reinhardtii |
| class III adenylyl cyclase | - |
Mus musculus |
| class III adenylyl cyclase | - |
Rattus norvegicus |
| class III adenylyl cyclase | - |
Saccharomyces cerevisiae |
| class III adenylyl cyclase | - |
Euglena gracilis |
| class III adenylyl cyclase | - |
Pseudomonas aeruginosa |
| class III adenylyl cyclase | - |
Trypanosoma brucei |
| class III adenylyl cyclase | - |
Dictyostelium discoideum |
| class III adenylyl cyclase | - |
Schizosaccharomyces pombe |
| class III adenylyl cyclase | - |
Caenorhabditis elegans |
| class III adenylyl cyclase | - |
Myxococcus xanthus |
| class III adenylyl cyclase | - |
Arthrospira platensis |
| class III adenylyl cyclase | - |
Ustilago maydis |
| class III adenylyl cyclase | - |
Chloroflexus aurantiacus |
| class III adenylyl cyclase | - |
Mycobacterium tuberculosis |
| class III adenylyl cyclase | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| class IIIb AC | - |
Euglena gracilis |
| class IIIb AC | - |
Pseudomonas aeruginosa |
| CyaA | - |
Myxococcus xanthus |
| cyaB1 | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| CyaB2 | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| cyaC | - |
Arthrospira platensis |
| cyaC | - |
Nostoc sp. PCC 7120 = FACHB-418 |
| More | 26 isoforms | Sinorhizobium meliloti |
| Rv1264 | - |
Mycobacterium tuberculosis |
| Rv1625c | - |
Mycobacterium tuberculosis |
| Rv1900c | - |
Mycobacterium tuberculosis |
| Rv3645 | - |
Mycobacterium tuberculosis |
| sAC | - |
Mus musculus |
| sAC | - |
Rattus norvegicus |
| soluble adenylyl cyclase | - |
Mus musculus |
| soluble adenylyl cyclase | - |
Rattus norvegicus |
pH Range
| pH Minimum | pH Maximum | Comment | Organism |
|---|---|---|---|
| 6 | 8 | upon a shift from pH 8 to 6, Rv1264 is activated 40fold, pH sensitivity is linked to the N-terminal domain | Mycobacterium tuberculosis |
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