PA4079 is a 229-residue classical short-chain dehydrogenase/reductase (SDR) of Pseudomonas aeruginosa with a Rossmann-fold NAD(P)-binding domain. Crystal structures of the apo enzyme and its NADP complex show that NADP binding orders the active-site substrate-specificity loop, and that ligand binding swings the Tyr183 side chain out of the active site. The purified enzyme reduces a broad range of carbonyl substrates with NAD(P)H and is classed as a carbonyl reductase. Its physiological substrate and role are unknown; it remains highly expressed during antibiotic exposure, and the authors speculate that it might reduce antimicrobial compounds.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004090 carbonyl reductase (NADPH) activity | IDA PMID:28524228 Structure and characterization of a NAD(P)H-dependent carbon... | ACCEPT | Summary: PseudoCAP IDA from the structure and activity characterisation of purified PA4079. Sole seed of the GO:0016616 IBD at PTN002388087. Reason: The paper measures activity of the purified enzyme on a broad range of carbonyl substrates and solves NADP-bound structures, which is direct support for an NADPH-dependent carbonyl reductase. The broad-specificity carbonyl reductase term fits an enzyme without a known physiological substrate. Supporting Evidence: PMID:28524228 Structural similarity and activity for a broad range of substrates indicate that PA4079 functions as a carbonyl reductase. PMID:28524228 we determined its crystal structure and confirmed it to be a NAD(P)-dependent short-chain dehydrogenase/reductase |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from PTN002388087, whose sole seed is this gene's PseudoCAP IDA to carbonyl reductase (NADPH) activity. The target appearing in its own WITH/FROM is expected. Reason: The IBD is sound; the generic NAD(P)-dependent CH-OH oxidoreductase term is a cautious and appropriate choice for a large cross-kingdom SDR clade with only one characterised member. For PA4079 itself the term is true but less specific than the evidence, so it is refined to GO:0004090, which the gene carries by IDA and which is a descendant (via GO:0008106). Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002388087 · PTN002388087 SUPPORTS TRANSFER QuickGO (2026-10-28) lists 369 GO:0016616 leaves (bacteria, fungi, algae, diatoms, oomycetes, a few arthropods); the worklist's older release had 27. PA4079 is the only characterised member. UniProtKB:Q9HWU9 · PA4079 SUPPORTS TRANSFER The target's own direct enzymology is the IBD seed; expected, not circular. Proposed replacements: carbonyl reductase (NADPH) activity Supporting Evidence: PMID:28524228 Structural similarity and activity for a broad range of substrates indicate that PA4079 functions as a carbonyl reductase. file:PSEAE/PA4079/PA4079-uniprot.txt SDR_fam |
| GO:0050661 NADP binding | IDA PMID:28524228 Structure and characterization of a NAD(P)H-dependent carbon... | NEW | Summary: NADP is bound in two crystal structures of PA4079 (PDB 5WQO, 5WQP), and its binding orders the active-site specificity loop. Reason: Direct structural evidence for the cofactor of the characterised NAD(P)H-dependent reductase; UniProt records 13 NADP(+)-binding residues derived from these structures. It is a supporting aspect of the core catalytic function. Supporting Evidence: PMID:28524228 Comparison of apo- and holo-PA4079 shows that NADP stabilizes the active site specificity loop file:PSEAE/PA4079/PA4079-uniprot.txt /ligand="NADP(+)" |
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Download this section (compressed HTML)Q: What is the physiological substrate of PA4079, and does it reduce antimicrobial compounds or host-derived carbonyls in vivo?
Experiment: Screen PA4079 against carbonyl-containing antibiotics and quorum-sensing or metabolic ketones/aldehydes, and compare antibiotic susceptibility and metabolite profiles of a PA4079 deletion mutant with wild type.
Type: enzyme substrate screen with genetic knockout phenotyping
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