id: Q9I4X2
gene_symbol: pqsB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:208964
  label: Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
    14847 / LMG 12228 / 1C / PRS 101 / PAO1)
description: >-
  PqsB (PA0997) is the non-catalytic subunit of the heterodimeric condensing enzyme
  PqsBC, which catalyzes the second step of 2-alkyl-4(1H)-quinolone (AQ/HAQ)
  biosynthesis in the Pseudomonas aeruginosa pqs quorum-sensing pathway. PqsBC
  couples 2-aminobenzoylacetate (2-ABA, made by PqsD) with an octanoyl group carried
  on the catalytic subunit PqsC to form 2-heptyl-4(1H)-quinolone (HHQ), the direct
  precursor of the Pseudomonas quinolone signal PQS. PqsB shares the beta-ketoacyl-ACP
  synthase III (FabH/KAS III) fold with PqsC but lacks the catalytic residues (the
  active-site Cys-129/His-269 are contributed by PqsC); it is nonetheless tightly
  associated with PqsC and required for the condensation reaction (PMID:24239007,
  PMID:26811339). PqsBC is thus an obligate heterodimer that is only functional when
  assembled. A pqsB mutant is defective in extracellular quinolone signal production
  (PMID:12426334).
references:
- id: PMID:24239007
  title: 'The end of an old hypothesis: the pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines
    derive from fatty acids, not 3-ketofatty acids.'
  findings:
  - statement: >-
      PqsB is tightly associated with PqsC and required for the condensation step;
      the octanoate group is carried on PqsC.
    supporting_text: >-
      the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC
      produces HHQ, the direct precursor of PQS. PqsB is tightly associated with PqsC
      and required for the second step.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PubMed-verified; establishes PqsB as the required partner of catalytic PqsC.
- id: PMID:26811339
  title: 'PqsBC, a Condensing Enzyme in the Biosynthesis of the Pseudomonas aeruginosa
    Quinolone Signal: CRYSTAL STRUCTURE, INHIBITION, AND REACTION MECHANISM.'
  findings:
  - statement: >-
      PqsBC has a unique heterodimeric arrangement; the catalytic active site
      (Cys-129, His-269) lies in PqsC, so PqsB is the non-catalytic subunit.
    supporting_text: >-
      does not form a catalytic triad with His-269 and Cys-129, and in its place a valine (Val-299) is present
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Crystal structure (PDB 5DWZ); shows the catalytic machinery resides in PqsC,
      supporting the contributes_to (not enables) status of PqsB for the activity.
- id: PMID:12426334
  title: Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa.
  findings:
  - statement: >-
      The pqsABCDE operon (including pqsB) is required for synthesis of the
      extracellular Pseudomonas quinolone signal.
    supporting_text: >-
      Functions required for extracellular quinolone signaling by Pseudomonas aeruginosa
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Experimental (IMP) genetic evidence for involvement of pqsB in quinolone signal biosynthesis.
- id: file:PSEAE/pqsB/pqsB-notes.md
  title: pqsB review notes (BGC project) with predicted-complex evidence
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Subcellular-location IEA, consistent with the experimental cytoplasmic
      localization (EXP, PMID:24239007) below and with PqsBC being a soluble
      cytoplasmic condensing enzyme.
    action: ACCEPT
    reason: Correct cellular component; corroborated by experimental evidence.
- term:
    id: GO:0016746
    label: acyltransferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro-based (IEA) acyltransferase activity from the condensing-enzyme
      (thiolase-like) signature. PqsB has this fold but is catalytically inactive:
      the active-site Cys-129/His-269 and the octanoyl substrate are carried by PqsC.
      The acyltransferase activity is a property of the assembled PqsBC heterodimer,
      catalyzed by PqsC, not enabled by PqsB on its own.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      Attributing the catalytic MF to the non-catalytic subunit over-annotates PqsB.
      PqsB contributes to (is required for) the activity of the PqsBC complex but does
      not itself catalyze acyl transfer; a contributes_to qualifier, or annotation of
      the activity to the PqsBC complex, would be more accurate.
    supported_by:
    - reference_id: PMID:26811339
      supporting_text: >-
        does not form a catalytic triad with His-269 and Cys-129, and in its place a valine (Val-299) is present
    - reference_id: PMID:24239007
      supporting_text: >-
        the decarboxylating coupling of 2-ABA to an octanoate group linked to PqsC
        produces HHQ
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:24239007
  qualifier: located_in
  review:
    summary: >-
      Experimental cytoplasmic localization, consistent with PqsB acting as part of
      the soluble cytoplasmic PqsBC condensing enzyme.
    action: ACCEPT
    reason: Experimentally supported cellular component.
- term:
    id: GO:0044550
    label: secondary metabolite biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:12426334
  qualifier: involved_in
  review:
    summary: >-
      Experimental (IMP) evidence that pqs genes, including pqsB, are required for
      extracellular quinolone signal synthesis. PqsB is required for the PqsBC
      condensation step and thus for HHQ/HAQ production.
    action: ACCEPT
    reason: >-
      Core biological process with direct experimental (mutant phenotype) support.
      This is the defining process for the gene.
    supported_by:
    - reference_id: PMID:24239007
      supporting_text: >-
        PqsB is tightly associated with PqsC and required for the second step
core_functions:
- description: >-
    Non-catalytic subunit of the PqsBC condensing enzyme (EC 2.3.1.230). PqsB does not
    itself catalyze acyl transfer (it lacks the catalytic Cys-129/His-269 of PqsC) but
    is an obligate partner required for the activity and stability of the catalytically
    competent PqsBC heterodimer, and hence for biosynthesis of the 2-alkyl-4(1H)-quinolone
    (HAQ) quorum-sensing signals (HHQ, the precursor of PQS) in the pqs pathway
    (PMID:24239007, PMID:26811339, PMID:12426334).
  contributes_to_molecular_function:
    id: GO:0016746
    label: acyltransferase activity
  directly_involved_in:
    - id: GO:0044550
      label: secondary metabolite biosynthetic process
  supported_by:
  - reference_id: PMID:26811339
    supporting_text: >-
      does not form a catalytic triad with His-269 and Cys-129, and in its place a valine (Val-299) is present
  - reference_id: PMID:24239007
    supporting_text: >-
      PqsB is tightly associated with PqsC and required for the second step
suggested_questions:
- question: >-
    Per GO guidelines the EC 2.3.1.230 activity is annotated to the catalytic subunit
    PqsC (enables); PqsB, being required but non-catalytic, is best represented with a
    contributes_to (not as a co-equal enabler) plus the protein-containing complex CC.
    Is the contributes_to warranted here, or should PqsB carry only the complex and
    process annotations?
suggested_experiments:
- description: >-
    Co-expression/co-purification and activity assays of PqsC alone versus the PqsBC
    heterodimer to quantify the requirement of PqsB for HHQ synthase activity and
    complex stability.