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Literature summary for 7.2.2.22 extracted from
- A novel P1B-type Mn2+-transporting ATPase is required for secreted protein metallation in mycobacteria (2013), J. Biol. Chem., 288, 11334-11347 .
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene ctpC, recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21 (DE3) pLysS pSJS1240, recombinant enzyme expression from pBAD TOPO vector carrying in Escherichia coli strain W3110 DELTAzntA cells. Quantitative RT-PCR enzyme expression analysis. Lack of functional complementation of Escherichia coli DELTAzntA by ctpC | Mycobacterium tuberculosis |
| gene ctpC, recombinant expression of C-terminally His6-tagged enzyme in Escherichia coli strain BL21 (DE3) pLysS pSJS1240. Quantitative RT-PCR enzyme expression analysis | Mycolicibacterium smegmatis |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| H697A | site-directed mutagenesis | Mycolicibacterium smegmatis |
| H699A | site-directed mutagenesis, the mutant shows no ATPase activity at saturating Mn2+ levels | Mycobacterium tuberculosis |
| additional information | a Zn2+ tolerance-decreased phenotype is oberseved in Mycobacterium tuberculosis strain H37Rv ctpC::hyg cells when grown at Zn2+ concentrations as low as 0.005 mM, but no changes are observed in the sensitivity to Cd2+. Presence of Co2+ or Cu2+ in the medium has no effect on the growth of these cells. Deletion of ctpC leads to cytoplasmic Mn2+ accumulation and a decrease in secreted Mn2+-bound proteins. A 4fold increase in cellular Mn2+ content is observed in the Mycobacterium tuberculosis ctpC mutant, along with a significant decrease in the Mn2+ bound to secreted proteins. The levels of Zn2+, Fe2+, or Cu2+ bound to secreted proteins are not affected in the Mycobacterium tuberculosis ctpC mutant strain. Fraction metal content of Mycobacterium tuberculosis strains, Mn2+ contents of wild-type and mutant enzymes, overview | Mycobacterium tuberculosis |
| additional information | the levels of Zn2+, Fe2+, or Cu2+ bound to secreted proteins are not affected in the Mycobacterium smegmatis ctpC mutant strain. Response of ctpC::hyg to metal and redox stressors | Mycolicibacterium smegmatis |
| S700A/S701A | site-directed mutagenesis | Mycolicibacterium smegmatis |
| S700A/S701A | site-directed mutagenesis, the mutant shows no ATPase activity at saturating Mn2+ levels | Mycobacterium tuberculosis |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| membrane | - |
Mycobacterium tuberculosis | 16020 | - |
| membrane | - |
Mycolicibacterium smegmatis | 16020 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Cu+ | slight activation at 10 nM | Mycobacterium tuberculosis |  |
| Cu2+ | about 28% activation compared to Mn2+ at 10 nM | Mycobacterium tuberculosis | |
| Mg2+ | required | Mycobacterium tuberculosis | |
| Mg2+ | required | Mycolicibacterium smegmatis | |
| Mn2+ | isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+ | Mycobacterium tuberculosis | |
| Mn2+ | isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+ | Mycolicibacterium smegmatis | |
| additional information | enzyme metal content analysis | Mycolicibacterium smegmatis | |
| additional information | enzyme metal content analysis. No or poor activation by Cd2+, Fe2+, and Fe3+ at 10 nM | Mycobacterium tuberculosis | |
| Ni2+ | slight activation at 10 nM | Mycobacterium tuberculosis | |
| Zn2+ | isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+ | Mycolicibacterium smegmatis | |
| Zn2+ | isolated CtpC has metal-dependent ATPase activity with a strong preference for Mn2+ over Zn2+, about 25% activation compared to Mn2+ at 10 nM | Mycobacterium tuberculosis | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + Mn2+[side 1] | Mycobacterium tuberculosis | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | Mycolicibacterium smegmatis | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | Mycolicibacterium smegmatis ATCC 700084 | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | Mycobacterium tuberculosis H37Rv | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | Mycobacterium tuberculosis ATCC 25618 | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | Mycolicibacterium smegmatis mc(2)155 | - |
ADP + phosphate + Mn2+[side 2] | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Mycobacterium tuberculosis | P9WPT5 | - |
- |
| Mycobacterium tuberculosis ATCC 25618 | P9WPT5 | - |
- |
| Mycobacterium tuberculosis H37Rv | P9WPT5 | - |
- |
| Mycolicibacterium smegmatis | I7GFC6 | Mycobacterium smegmatis | - |
| Mycolicibacterium smegmatis ATCC 700084 | I7GFC6 | Mycobacterium smegmatis | - |
| Mycolicibacterium smegmatis mc(2)155 | I7GFC6 | Mycobacterium smegmatis | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21 (DE3) pLysS pSJS1240 by ultracentrifugation at 229000 x g, nickel affinity chromatography, and ultrafiltration | Mycolicibacterium smegmatis |
| recombinant C-terminally His6-tagged enzyme from Escherichia coli strain BL21 (DE3) pLysS pSJS1240 by ultracentrifugation at 229000 x g, nickel affinity chromatography, and ultrafiltration, the tag is cleaved by TEV protease | Mycobacterium tuberculosis |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + H2O + Mn2+[side 1] | - |
Mycobacterium tuberculosis | ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | - |
Mycolicibacterium smegmatis | ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | - |
Mycolicibacterium smegmatis ATCC 700084 | ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | - |
Mycobacterium tuberculosis H37Rv | ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | - |
Mycobacterium tuberculosis ATCC 25618 | ADP + phosphate + Mn2+[side 2] | - |
? | |
| ATP + H2O + Mn2+[side 1] | - |
Mycolicibacterium smegmatis mc(2)155 | ADP + phosphate + Mn2+[side 2] | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| ? | x * 80000, recombinant enzyme, SDS-PAGE | Mycobacterium tuberculosis |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| ctpC | - |
Mycobacterium tuberculosis |
| ctpC | - |
Mycolicibacterium smegmatis |
| P1B-type Mn2+-transporting ATPase | - |
Mycobacterium tuberculosis |
| P1B-type Mn2+-transporting ATPase | - |
Mycolicibacterium smegmatis |
Temperature Optimum [°C]
| Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
|---|---|---|---|
| 37 | - |
assay at | Mycobacterium tuberculosis |
| 37 | - |
assay at | Mycolicibacterium smegmatis |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8 | - |
assay at | Mycobacterium tuberculosis |
| 8 | - |
assay at | Mycolicibacterium smegmatis |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Mycobacterium tuberculosis | |
| ATP | - |
Mycolicibacterium smegmatis | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | key metal-coordinating residues and the overall structure of CtpC are distinct from Zn2+-ATPases | Mycobacterium tuberculosis |
| evolution | key metal-coordinating residues and the overall structure of CtpC are distinct from Zn2+-ATPases | Mycolicibacterium smegmatis |
| malfunction | mutation of CtpC leads to a decrease of Mn2+ bound to secreted proteins and of the activity of secreted Fe/Mn-superoxide dismutase, especially in Mycobacterium smegmatis | Mycolicibacterium smegmatis |
| malfunction | mutation of CtpC leads to a decrease of Mn2+ bound to secreted proteins and of the activity of secreted Fe/Mn-superoxide dismutase. CtpC deficiency renders Mycobacterium tuberculosis sensitive to Zn2+ and oxidative stress | Mycobacterium tuberculosis |
| metabolism | link between the observed Mn2+-dependent ATPase activity and the binding of Mn2+ to a transmembrane transport site distinct from those in Cu+- or Zn2+-ATPases | Mycobacterium tuberculosis |
| additional information | importance of the distinct HXXSS sequence in TM8 of Mycobacterium tuberculosis CtpC | Mycobacterium tuberculosis |
| physiological function | transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-type Mn2+-transporting ATPase is required for secreted protein metallation in mycobacteria and for Mycobacterium tuberculosis survival in a mouse model (infection of C57BL/6 female mice). CtpC is a unique Mn2+-ATPase | Mycobacterium tuberculosis |
| physiological function | transition metals are central for bacterial virulence and host defense. P1B-ATPases are responsible for cytoplasmic metal efflux and play roles either in limiting cytosolic metal concentrations or in the maturation of secreted metalloproteins. The P1B-type Mn2+-transporting ATPase is required for secreted protein metallation in mycobacteria. CtpC is a unique Mn2+-ATPase | Mycolicibacterium smegmatis |
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Release 2023.1 (January 2023)
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