PA4400 is the MutT 8-oxo-dGTP diphosphatase of P. aeruginosa, part of the GO (8-oxoguanine) system with MutM and MutY that prevents mutations caused by oxidised guanine. Its N-terminal Nudix hydrolase domain hydrolyses 8-oxo-dGTP (and, by homology with E. coli MutT, 8-oxo-GTP) to the monophosphate and pyrophosphate, removing the mutagenic nucleotide from the precursor pool before it can be misincorporated opposite adenine. The cloned gene complements the high mutation frequency of an E. coli mutT mutant, and the N-terminal part of the protein is necessary and sufficient for this activity. The protein carries a C-terminal domain related to thiamine phosphate synthase / TenI whose function is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006281 DNA repair | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000755027 (MutT clade, 27 leaf IBAs in 22 taxa), seeded by E. coli MutT (P08337, EcoCyc EXP, UniProt IC) and PA4400 itself (PseudoCAP IDA, PMID:12445642). The self-seed is expected, not circular. Reason: GO annotates MutT-type 8-oxo-dGTPases to DNA repair (E. coli MutT and human NUDT1 carry it), as the antimutator arm of the GO system. The IBD stands on E. coli MutT alone and the term suits the clade. Supporting Evidence: PMID:12445642 The three genes, when cloned in a plasmid, were able to complement the high mutation frequency of the corresponding Escherichia coli deficient strains. |
| GO:0006281 DNA repair | IDA PMID:12445642 Characterization of the GO system of Pseudomonas aeruginosa. | ACCEPT | Summary: PseudoCAP row, seed of the PTN000755027 DNA repair IBD. Seed verdict SOUND (term), with an evidence-code problem. Reason: Complementation of the E. coli mutT mutator phenotype supports the GO system role, and the term follows GO practice for MutT. The abstract reports heterologous genetic complementation, which is IGI rather than IDA. Supporting Evidence: PMID:12445642 The three genes, when cloned in a plasmid, were able to complement the high mutation frequency of the corresponding Escherichia coli deficient strains. |
| GO:0006281 DNA repair | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the MutT family signatures. Reason: Consistent with the IBA and the complementation evidence. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0008413 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000755027, seeded by E. coli MutT (several IDAs). Reason: E. coli MutT hydrolyses 8-oxo-GTP as well as 8-oxo-dGTP, and PA4400 has the conserved Nudix MutT domain, so the inference is reasonable. It has not been tested for PA4400, and the antimutator function rests on the deoxy substrate. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0008413 8-oxo-7,8-dihydroguanosine triphosphate pyrophosphatase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO from the MutT signature. Reason: Same claim and action as the IBA row. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0016787 hydrolase activity | IDA PMID:12445642 Characterization of the GO system of Pseudomonas aeruginosa. | TOO GENERAL | Summary: PseudoCAP row for the 8-oxo-dGTP hydrolase activity of the N-terminal part. Reason: True but uninformative. The paper attributes the 8-oxo-dGTP hydrolase activity to the N-terminal Nudix part, which is GO:0035539, accepted in this review and a descendant of hydrolase activity. The abstract suggests this too was judged by complementation, so the IDA code may also be IGI. Supporting Evidence: PMID:12445642 Our results also demonstrated that the N-terminal part of the protein is necessary and sufficient for the 8-oxodGTP hydrolase activity. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000120 | TOO GENERAL | Summary: Combined IEA hydrolase activity. Reason: True but uninformative. 8-oxo-dGTP pyrophosphatase activity (GO:0035539), accepted here, is a descendant and entails it. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0035539 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000755027, seeded by E. coli MutT (IDA). Reason: The defining MutT activity. The P. aeruginosa gene complements E. coli mutT, and the paper assigns the 8-oxo-dGTP hydrolase activity to its N-terminal Nudix part. Supporting Evidence: PMID:12445642 Our results also demonstrated that the N-terminal part of the protein is necessary and sufficient for the 8-oxodGTP hydrolase activity. |
| GO:0035539 8-oxo-7,8-dihydrodeoxyguanosine triphosphate pyrophosphatase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC mapping (3.6.1.55). Reason: Consistent with the IBA and the complementation evidence. Supporting Evidence: PMID:12445642 Our results also demonstrated that the N-terminal part of the protein is necessary and sufficient for the 8-oxodGTP hydrolase activity. |
| GO:0044715 8-oxo-dGDP phosphatase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000755027, seeded by E. coli MutT (IDA, PMID:15850400). Reason: E. coli MutT also hydrolyses 8-oxo-dGDP; plausible for PA4400 by descent but untested, and secondary to the 8-oxo-dGTPase activity. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0044716 8-oxo-GDP phosphatase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000755027, seeded by E. coli MutT (IDA, PMID:15850400). Reason: As for 8-oxo-dGDP phosphatase: shown for E. coli MutT, plausible by descent, untested for PA4400 and secondary. Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt Mutator_MutT |
| GO:0046872 metal ion binding | IEA GO_REF:0000104 | MODIFY | Summary: UniRule transfer of metal ion binding. Reason: Correct but general. Nudix MutT enzymes use Mg2+ bound by the Nudix box glutamates, and the PIRSR cofactor rule gives Mg2+ for this entry. Proposed replacements: magnesium ion binding Supporting Evidence: file:PSEAE/PA4400/PA4400-uniprot.txt PIRSR:PIRSR603561-2 |
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Download this section (compressed HTML)Q: Does the C-terminal TenI/thiamine-phosphate synthase-like domain of PA4400 have any catalytic activity in thiamine metabolism, or is it a degenerate domain?
Experiment: Purify PA4400 and its isolated N- and C-terminal domains; measure hydrolysis of 8-oxo-dGTP, 8-oxo-GTP and 8-oxo-dGDP, and test the C-terminal domain for thiazole tautomerase (TenI) or thiamine-phosphate synthase activity.
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