PA4975 is a soluble flavodoxin-fold NAD(P)H:quinone oxidoreductase of Pseudomonas aeruginosa, the bacterial counterpart of the mammalian NQO1/NQO2 (DT-diaphorase) family; its sequence is most similar to human NQO2. As one of five P. aeruginosa quinone oxidoreductases tested, it reduces quinones in vitro by a two-electron route with little semiquinone formation, a property linked to antioxidant defence, although its overexpression did not protect against H2O2. The gene lies at the end of the arginine-inducible PA4981-PA4975 cluster next to the arginine transaminase gene aruH, but no role in arginine catabolism has been shown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000117 | TOO GENERAL | Summary: True but uninformative. Reason: GO:0003955 NAD(P)H dehydrogenase (quinone) activity, accepted in this review, is_a catalytic activity. Supporting Evidence: PMID:25085734 In in vitro assays, each enzyme was shown to reduce quinone substrates with only minimal semiquinone formation. |
| GO:0003955 NAD(P)H dehydrogenase (quinone) activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBD at PTN000024521, seeded by human, mouse and rat NQO1 and by PA4975's own PseudoCAP row. Reason: PA4975 in its own WITH/FROM is expected. The activity is reported for the purified P. aeruginosa enzyme, and the flavodoxin-like NQO fold and PANTHER subfamily agree. Supporting Evidence: PMID:25085734 In in vitro assays, each enzyme was shown to reduce quinone substrates with only minimal semiquinone formation. PMID:24915188 Recent data have shown that PA0949, PA1204, PA2580 and PA4975, have NAD(P)H quinone oxidoreductase activities [75]. |
| GO:0003955 NAD(P)H dehydrogenase (quinone) activity | IMP PMID:25085734 Pseudomonas aeruginosa MdaB and WrbA are water-soluble two-e... | ACCEPT | Summary: PseudoCAP IMP and one of four seeds of the PTN000024521 GO:0003955 IBD. The paper assayed purified P. aeruginosa orthologs of five quinone oxidoreductases, including the NQO1 ortholog. Seed verdict SOUND for the term; the evidence code should be IDA. Reason: The activity is supported by the in vitro assays reported in the abstract, and Ryan et al. 2014 name PA4975 among the P. aeruginosa enzymes with this activity. The evidence is a direct enzyme assay, not a mutant phenotype, so the IMP code is recorded as a source defect; the claim is accepted. Supporting Evidence: PMID:25085734 In in vitro assays, each enzyme was shown to reduce quinone substrates with only minimal semiquinone formation. PMID:24915188 Recent data have shown that PA0949, PA1204, PA2580 and PA4975, have NAD(P)H quinone oxidoreductase activities [75]. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosol IBD from human NQO1 and NQO2. PA4975 is a water-soluble enzyme with no signal peptide or transmembrane segment. Reason: The paper describes these P. aeruginosa enzymes as water-soluble, and the protein has no targeting signal, so a cytosolic location in a bacterium is the expected inheritance from the NQO clade. Supporting Evidence: PMID:25085734 Water-soluble quinone oxidoreductases capable of reducing quinone substrates via a concerted two-electron mechanism |
Loading supporting content…
Download this section (compressed HTML)Q: PA4975 is closest to human NQO2, which prefers dihydronicotinamide riboside to NAD(P)H. Which reduced cofactor does PA4975 use in vivo, and what is its physiological quinone or other electron acceptor?
Q: Does PA4975, co-induced with the arginine transaminase genes, have any role in arginine catabolism or oxidative-stress protection in a katA background?
Experiment: Steady-state kinetics of purified PA4975 with NADH, NADPH and dihydronicotinamide riboside against menadione, benzoquinone and ubiquinone analogues, with dicoumarol inhibition, to place it on the NQO1/NQO2 axis.
Type: enzyme kinetics
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)