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Literature summary for 4.6.1.1 extracted from
- Mycobacterial adenylyl cyclases: biochemical diversity and structural plasticity (2006), FEBS Lett., 580, 3344-3352.
Activating Compound
| Activating Compound | Comment | Organism | Structure |
|---|---|---|---|
| bicarbonate | stimulates purified Rv1319c catalytic domain | Mycobacterium tuberculosis |  |
| additional information | activity of Rv1264 is be regulated by pH | Mycobacterium tuberculosis | |
| additional information | HAMP domain of Rv3645 activates adenylyl cyclase activity | Mycobacterium tuberculosis | |
| NaCl | Rv1647 is slightly activated at 500 mM | Mycobacterium tuberculosis | |
Application
| Application | Comment | Organism |
|---|---|---|
| additional information | Rv0386 shows both adenylyl and a guanylyl cyclase side-activity | Mycobacterium tuberculosis |
| additional information | Rv1120c is a pseudogene in Mycobacterium tuberculosis | Mycobacterium tuberculosis |
| additional information | Rv1318c has a HAMP domain | Mycobacterium tuberculosis |
| additional information | Rv1319c has a HAMP domain | Mycobacterium tuberculosis |
| additional information | Rv1320c has aHAMP domain | Mycobacterium tuberculosis |
| additional information | Rv1625c has the highest sequence similarity with the mammalian enzymes | Mycobacterium tuberculosis |
| additional information | Rv1647 adenylyl cyclase has a cyclase domain that is more closely related to fungal and protist cyclases | Mycobacterium tuberculosis |
| additional information | Rv3645 has a HAMP domain | Mycobacterium tuberculosis |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
- |
Mycobacterium avium |
- |
Mycobacterium leprae |
| overexpression of Rv1625c in Escherichia coli and expressed in mammalian cells | Mycobacterium tuberculosis |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| crystal structure of the cyclase domain of Rv1900c in the absence and presence of an ATP analogue, active form contains the metal and the nucleotide only at one of the two active sites, two active sites, though exactly identical in sequence, are structurally distinct | Mycobacterium tuberculosis |
| Rv1625c mutant K296E/F363R/D365C, significant interfacial clashes which preclude dimerization | Mycobacterium tuberculosis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| D147A | Rv1647 mutant, mutation of first metal-binding residue, barely active | Mycobacterium tuberculosis |
| D241C | Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity | Mycobacterium tuberculosis |
| D256A | Rv1625c mutant, mutation of the metal-binding residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647 | Mycobacterium tuberculosis |
| D256A/D300A | mixture of artificial C2-like mutants of Rv1625c, reconstitutes an active enzyme | Mycobacterium tuberculosis |
| D300A | Rv1625c mutant, mutation of the metal-binding residue, leads to significant decrease in adenylyl cyclase activity, can heterodimerize and reconstitute activity with the Paramaecium guanylyl cyclase C1-like domain, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647 | Mycobacterium tuberculosis |
| D365A | Rv1625c mutant, mutation of the substrate specifying residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647 | Mycobacterium tuberculosis |
| D365C | Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity | Mycobacterium tuberculosis |
| F363R | Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity | Mycobacterium tuberculosis |
| K187E | Rv1647 mutant, mutation of C1-like substrate specifying residues, barely active, does not lead to a gain in guanylyl cyclase activity | Mycobacterium tuberculosis |
| K187E/D241C | Rv1647 mutant, mixture of artificial C1-like mutants, reconstitutes high adenylyl cyclase activity, does not lead to a gain in guanylyl cyclase activity | Mycobacterium tuberculosis |
| K296A | Rv1625c mutant, mutation of the substrate specifying residue, leads to significant decrease in adenylyl cyclase activity, can not reconstitute activity with C1 or C2 domains of the mammalian adenylyl cyclase isoforms or with Rv1647 | Mycobacterium tuberculosis |
| K296A/D365A/R376A | mixture of artificial C1-like mutants of Rv1625c, reconstitutes an active enzyme | Mycobacterium tuberculosis |
| K296E | Rv1625c mutant, does not result in a gain of guanylyl cyclase activity, but leads to severely compromised adenylyl cyclase activity | Mycobacterium tuberculosis |
| K296E/F363R/D365C | Rv1625c mutant, is largely monomeric, has neither adenylyl cyclase or guanylyl cyclase activity, unable to heterodimerize with the wild-type protein | Mycobacterium tuberculosis |
| additional information | knock-out strain lacking Rv1625c is as virulent as the wild-type strain in the mouse model of tuberculosis infection | Mycobacterium tuberculosis |
| additional information | mutation of N342 does not affect adenylyl cyclase activity in Rv1900c | Mycobacterium tuberculosis |
| additional information | strain lacking the Rv1264-like cyclase is unable to execute an apparently cAMP and acid pH-dependent differentiation pathway | Streptomyces coelicolor |
| Q57K/N106D | Rv0386 mutant, abolishes activity | Mycobacterium tuberculosis |
| R376A | Rv1625c mutant, mutation of the transition state stabilizing residue, leads to significant decrease in adenylyl cyclase activity | Mycobacterium tuberculosis |
| R43A/R44G | Rv1625c mutant, mutation of two arginine residues in the extreme N-terminal region, preceding the first transmembrane helix, severely compromises adenylyl activity of the full length protein | Mycobacterium tuberculosis |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 2',5'-dideoxyadenosine 3'-monophosphate | - |
Mycobacterium avium | |
| 2',5'-dideoxyadenosine-3'-triphosphate | - |
Mycobacterium avium | |
| additional information | HAMP domain of Rv1319c inhibits adenylyl cyclase activity; no inhibition of Rv1625c by P-site ATP analogues; the first ca. 200 amino acid region of Rv1264 holoenzyme is auto-inhibitory | Mycobacterium tuberculosis |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cell wall | - |
Mycobacterium tuberculosis | 5618 | - |
| cytosol | - |
Mycobacterium tuberculosis | 5829 | - |
| membrane | - |
Mycobacterium tuberculosis | 16020 | - |
| membrane | Rv1625c is a six-transmembrane protein with a single class III cyclase domain | Mycobacterium tuberculosis | 16020 | - |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Brevibacterium sp. | - |
- |
- |
| Mycobacterium avium | - |
- |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73S12 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73T75 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73WG5 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73WI8 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73X03 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73X69 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73XQ9 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q73Y78 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q740J3 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q740N2 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q740R3 | - |
- |
| Mycobacterium avium subsp. paratuberculosis | Q744B5 | - |
- |
| Mycobacterium avium TN104 | - |
- |
- |
| Mycobacterium leprae | - |
- |
- |
| Mycobacterium marinum | - |
- |
- |
| Mycobacterium tuberculosis | O06362 | - |
- |
| Mycobacterium tuberculosis | O06572 | - |
- |
| Mycobacterium tuberculosis | O07732 | - |
- |
| Mycobacterium tuberculosis | O53213 | - |
- |
| Mycobacterium tuberculosis | O53720 | - |
- |
| Mycobacterium tuberculosis | P71914 | - |
- |
| Mycobacterium tuberculosis | P94982 | - |
- |
| Mycobacterium tuberculosis | P9WM05 | - |
- |
| Mycobacterium tuberculosis | P9WMU7 | - |
- |
| Mycobacterium tuberculosis | P9WMV1 | - |
- |
| Mycobacterium tuberculosis | P9WQ29 | - |
- |
| Mycobacterium tuberculosis | P9WQ31 | - |
- |
| Mycobacterium tuberculosis | P9WQ33 | - |
- |
| Mycobacterium tuberculosis | P9WQ35 | - |
- |
| Mycobacterium tuberculosis | Q11028 | - |
- |
| Mycobacterium tuberculosis H37Rv | O53213 | - |
- |
| Mycobacterium tuberculosis H37Rv | O53720 | - |
- |
| Mycobacterium tuberculosis H37Rv | P71914 | - |
- |
| Mycobacterium tuberculosis H37Rv | P94982 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WM05 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WMU7 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WMV1 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WQ29 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WQ31 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WQ33 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WQ35 | - |
- |
| Mycobacterium tuberculosis variant bovis | - |
- |
- |
| Mycolicibacterium smegmatis | - |
- |
- |
| Streptomyces coelicolor | - |
- |
- |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
- |
Mycobacterium leprae |
| full length Rv1264 protein purified to homogeneity | Mycobacterium tuberculosis |
| full length Rv1625c protein purified to homogeneity | Mycobacterium tuberculosis |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP | - |
Mycobacterium tuberculosis | 3',5'-cAMP + diphosphate | - |
? | |
| ATP | - |
Mycobacterium tuberculosis H37Rv | 3',5'-cAMP + diphosphate | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| dimer | - |
Mycobacterium tuberculosis |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| class III adenylyl cyclase | - |
Mycolicibacterium smegmatis |
| class III adenylyl cyclase | - |
Mycobacterium avium |
| class III adenylyl cyclase | - |
Mycobacterium leprae |
| class III adenylyl cyclase | - |
Streptomyces coelicolor |
| class III adenylyl cyclase | - |
Brevibacterium sp. |
| class III adenylyl cyclase | - |
Mycobacterium tuberculosis variant bovis |
| class III adenylyl cyclase | - |
Mycobacterium marinum |
| class III adenylyl cyclase | - |
Mycobacterium tuberculosis |
| class III adenylyl cyclase | - |
Mycobacterium avium subsp. paratuberculosis |
| Ma1120 | functional orthologue of Rv1120c | Mycobacterium avium |
| MAP0426c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP1279c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP1318c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP1357 | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP2079 | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP2250c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP2440 | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP2507c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP2672 | functional orthologue of Rv1120c | Mycobacterium avium subsp. paratuberculosis |
| MAP2695c | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP3844 | - |
Mycobacterium avium subsp. paratuberculosis |
| MAP4266 | - |
Mycobacterium avium subsp. paratuberculosis |
| ML1399 | Rv1647 orthologue | Mycobacterium leprae |
| MM0123 | - |
Mycobacterium marinum |
| MM0157 | - |
Mycobacterium marinum |
| MM0286 | - |
Mycobacterium marinum |
| MM0666 | - |
Mycobacterium marinum |
| MM0730 | - |
Mycobacterium marinum |
| MM0935 | - |
Mycobacterium marinum |
| MM1414 | - |
Mycobacterium marinum |
| MM2428 | - |
Mycobacterium marinum |
| MM2454 | - |
Mycobacterium marinum |
| MM2550 | - |
Mycobacterium marinum |
| MM2962 | - |
Mycobacterium marinum |
| MM3042 | - |
Mycobacterium marinum |
| MM3043 | - |
Mycobacterium marinum |
| MM3257 | - |
Mycobacterium marinum |
| MM3505 | - |
Mycobacterium marinum |
| MM3522 | - |
Mycobacterium marinum |
| MM3640 | - |
Mycobacterium marinum |
| MM3755 | - |
Mycobacterium marinum |
| MM3757 | - |
Mycobacterium marinum |
| MM3795 | - |
Mycobacterium marinum |
| MM4078 | - |
Mycobacterium marinum |
| MM4079 | - |
Mycobacterium marinum |
| MM4080 | - |
Mycobacterium marinum |
| MM4120 | - |
Mycobacterium marinum |
| MM4173 | - |
Mycobacterium marinum |
| MM4340 | - |
Mycobacterium marinum |
| MM4370 | - |
Mycobacterium marinum |
| MM4438 | - |
Mycobacterium marinum |
| MM5137 | - |
Mycobacterium marinum |
| MM5254 | - |
Mycobacterium marinum |
| MM5257 | - |
Mycobacterium marinum |
| MSMEG0218 | - |
Mycolicibacterium smegmatis |
| MSMEG0536 | - |
Mycolicibacterium smegmatis |
| MSMEG3253 | - |
Mycolicibacterium smegmatis |
| MSMEG3579 | - |
Mycolicibacterium smegmatis |
| MSMEG3786 | - |
Mycolicibacterium smegmatis |
| MSMEG4282 | - |
Mycolicibacterium smegmatis |
| MSMEG4472 | - |
Mycolicibacterium smegmatis |
| MSMEG4909 | - |
Mycolicibacterium smegmatis |
| MSMEG5003 | - |
Mycolicibacterium smegmatis |
| MSMEG6117 | - |
Mycolicibacterium smegmatis |
| Rv0386 | - |
Mycobacterium tuberculosis |
| Rv0891c | - |
Mycobacterium tuberculosis |
| Rv1120c | - |
Mycobacterium tuberculosis |
| Rv1264 | - |
Mycobacterium tuberculosis |
| Rv1318c | - |
Mycobacterium tuberculosis |
| Rv1319c | - |
Mycobacterium tuberculosis |
| Rv1320c | - |
Mycobacterium tuberculosis |
| Rv1358 | - |
Mycobacterium tuberculosis |
| Rv1359 | - |
Mycobacterium tuberculosis |
| Rv1625c | - |
Mycobacterium tuberculosis |
| Rv1647 | - |
Mycobacterium tuberculosis |
| Rv1900c | - |
Mycobacterium tuberculosis |
| Rv2212 | - |
Mycobacterium tuberculosis |
| Rv2435c | - |
Mycobacterium tuberculosis |
| Rv2488c | - |
Mycobacterium tuberculosis |
| Rv3645 | - |
Mycobacterium tuberculosis |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| additional information | - |
Rv1647 has its pH optimum in the alkaline pH range | Mycobacterium tuberculosis |
pH Range
| pH Minimum | pH Maximum | Comment | Organism |
|---|---|---|---|
| 5.5 | 8 | the Rv1264 holoenzyme shows higher adenylyl cyclase activity at pH 6.0. In contrast, the purified cyclase domain shows similar activities at both pH 5.5 and pH 8.0, pH sensing is not a property of any single amino acid in Rv1264 but a property of a network of interactions between the N-terminal and cyclase domains | Mycobacterium tuberculosis |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.00075 | - |
- |
Mycobacterium avium | 2',5'-dideoxyadenosine-3'-triphosphate | |
| 0.05 | - |
- |
Mycobacterium avium | 2',5'-dideoxyadenosine 3'-monophosphate | |
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