parE (PA4967) encodes ParE, the B subunit of DNA topoisomerase IV. ParE forms a ParC2ParE2 heterotetramer with ParC (PA4964). ParE carries the GHKL ATPase (HATPase_c) and Toprim domains and supplies ATP-driven strand-passage energy, while ParC performs DNA binding, cleavage and rejoining. Topoisomerase IV is a type IIA topoisomerase that makes a transient double-strand break, passes a second duplex through it and reseals it. Its main role is decatenating replicated daughter chromosomes so that they can segregate; it also relaxes supercoiled DNA but does not introduce negative supercoils. P. aeruginosa topoisomerase IV, reconstituted from separately purified ParC and ParE, shows ATP-dependent decatenation and relaxation activity but no supercoiling activity. It is a secondary target of fluoroquinolones, being 5-8 times less sensitive than DNA gyrase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: DNA binding from the UniRule/keyword pipeline. Reason: The topoisomerase IV holoenzyme binds DNA, and the ParE Toprim domain contributes to the DNA-gate; most DNA binding is by ParC. The term is correct for the complex but peripheral to ParE's ATPase role. Supporting Evidence: file:PSEAE/parE/parE-uniprot.txt Pfam; PF01751; Toprim; 1. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IBA GO_REF:0000033 | ACCEPT | Summary: Type II (ATP-hydrolysing) topoisomerase activity by IBA from PTN000018885 (GyrB/ParE/eukaryotic Top2 node); sound. Reason: Agrees with the reconstituted-enzyme assay on this gene. The node's other seeds (E. coli GyrB, M. tuberculosis GyrB, Arabidopsis GyrB, P. falciparum Top2) are directly assayed. P. aeruginosa ParE among the sources reflects its own IDA. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA, a seed of the PTN000018885 IBD. ParC and ParE were purified separately (as MBP fusions) and the reconstituted enzyme had ATP-dependent decatenation and relaxation activity. Reason: Full text read. Direct biochemical evidence for the holoenzyme that ParE is part of. The activity requires both subunits, and ParE supplies the ATPase. Supporting Evidence: PMID:10049263 The putative ParC and ParE proteins were overexpressed and separately purified by use of a fusion system with a maltose-binding protein, and their enzymatic properties were examined. PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0003918 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 5.6.2.2 mapping; consistent. Reason: Same claim as the IDA and IBA rows. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: ATP binding of the GHKL ATPase domain. Reason: Correct (HATPase_c domain; the activity is ATP-dependent), but a substrate-binding term subsumed by the ATP-hydrolysing topoisomerase activity. Supporting Evidence: file:PSEAE/parE/parE-uniprot.txt Pfam; PF02518; HATPase_c; 1. |
| GO:0005694 chromosome | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Chromosome location from InterPro. Reason: Topoisomerase IV acts on chromosomal DNA during replication and segregation, so the location is plausible. It is peripheral to the function and was not assayed directly. Supporting Evidence: file:PSEAE/parE/parE-uniprot.txt Performs the decatenation events required during the replication of a circular DNA molecule. |
| GO:0006265 DNA topological change | IBA GO_REF:0000033 | ACCEPT | Summary: DNA topological change by IBA from PTN000018885; sound. Reason: Agrees with the IDA on this gene. The other seed, E. coli GyrB, is directly characterised. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0006265 DNA topological change | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA, a seed of the PTN000018885 IBD. Decatenation and relaxation by reconstituted topoisomerase IV. Reason: Full text read. Decatenation and relaxation are DNA topological changes catalysed by the enzyme itself. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0006265 DNA topological change | IEA GO_REF:0000120 | ACCEPT | Summary: DNA topological change from the UniRule pipeline; consistent. Reason: Same claim as the IDA and IBA rows. Supporting Evidence: PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV, and relaxing activities but had no supercoiling activity. |
| GO:0007059 chromosome segregation | IEA GO_REF:0000104 | ACCEPT | Summary: Chromosome segregation, from the HAMAP-based rule. Reason: Decatenation of replicated chromosomes by topoisomerase IV is the step that lets daughter chromosomes separate. The enzyme does the work of that step, as established for E. coli and encoded in HAMAP MF_00938. P. aeruginosa ParE decatenates in vitro. Supporting Evidence: file:PSEAE/parE/parE-uniprot.txt Topoisomerase IV is essential for chromosome segregation. PMID:10049263 The reconstituted enzyme had ATP-dependent decatenation activity, which is the main catalytic activity of bacterial topoisomerase IV |
| GO:0009330 DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex | IBA GO_REF:0000033 | TOO GENERAL | Summary: Type II topoisomerase complex by IBA from PTN000018885. Correct, but this review accepts the more specific DNA topoisomerase IV complex. Reason: GO:0009340 DNA topoisomerase IV complex (IDA row, accepted) is_a GO:0009330. The node term is right at node level, where it must cover both gyrase and topoisomerase IV B subunits; for ParE itself it is entailed. |
| GO:0009340 DNA topoisomerase IV complex | IDA PMID:10049263 Cloning, expression, and enzymatic characterization of Pseud... | ACCEPT | Summary: PseudoCAP IDA; supports the PTN000018885 GO:0009330 IBD as a descendant term. Activity needed the reconstitution of ParC and ParE. Reason: Full text read. Topoisomerase IV activity was reconstituted from the purified ParC and ParE subunits. The complex was not isolated as such, but the reconstitution is functional evidence for membership, in line with the HAMAP subunit statement. Supporting Evidence: PMID:10049263 The putative ParC and ParE proteins were overexpressed and separately purified by use of a fusion system with a maltose-binding protein, and their enzymatic properties were examined. file:PSEAE/parE/parE-uniprot.txt Heterotetramer composed of ParC and ParE. |
| GO:0051276 chromosome organization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Chromosome organization from ARBA. Reason: True in a broad sense (topoisomerase IV resolves chromosome catenanes and supercoils), but GO:0007059 chromosome segregation is not its descendant, so the row is not entailed. It is broader and less informative than chromosome segregation and DNA topological change. Supporting Evidence: file:PSEAE/parE/parE-uniprot.txt It relaxes supercoiled DNA. |
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Download this section (compressed HTML)Q: Do ParE mutations contribute to fluoroquinolone resistance in clinical P. aeruginosa isolates once gyrA/gyrB mutations are present, as expected for a secondary target?
Experiment: Measure decatenation by topoisomerase IV reconstituted with ParE variants from resistant clinical isolates, alongside fluoroquinolone IC50 values.
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