pqqA

UniProt ID: C5CPT7
Organism: Variovorax paradoxus S110
Review Status: COMPLETE
📝 Provide Detailed Feedback

Gene Description

PqqA (Vapar_3057, C5CPT7) in Variovorax paradoxus S110 is the 24-amino-acid ribosomally synthesized precursor peptide (MKWETPTATDLRFGFEITMYVSAR; HAMAP MF_00656, InterPro IPR011725, NCBIfam TIGR02107) for pyrroloquinoline quinone (PQQ) biosynthesis. Rather than functioning as a catalytic enzyme, PqqA serves as the polypeptide substrate of the PQQ biosynthetic pathway: its conserved glutamate (Glu16) and tyrosine (Tyr20) residues are bound by the peptide chaperone PqqD and cross-linked via an intramolecular carbon-carbon bond by the radical SAM cyclase PqqE, followed by proteolytic excision and oxidative ring maturation by PqqB and PqqC to yield the mature PQQ redox cofactor.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0018189 pyrroloquinoline quinone biosynthetic process
IEA
GO_REF:0000120 		ACCEPT
Reason: PqqA (Vapar_3057, C5CPT7) is the 24-residue ribosomally synthesized precursor peptide that supplies the conserved Glu16 and Tyr20 residues cross-linked by PqqD/PqqE and excised to construct pyrroloquinoline quinone (PQQ); this biological process term accurately captures its core pathway role.
Supporting Evidence:
UniProtKB:C5CPT7
CC -!- FUNCTION: Required for coenzyme pyrroloquinoline quinone (PQQ) CC biosynthesis. PQQ is probably formed by cross-linking a specific CC glutamate to a specific tyrosine residue and excising these residues CC from the peptide. {ECO:0000255|HAMAP-Rule:MF_00656}.
PMID:32731194
The pqqA is translated into a short peptide that contains the fully conserved residues, glutamate and tyrosine; site-direct mutagenesis identified these two residues on PqqA as the best candidate for the precursor to PQQ (Figure 2A).[31]
GO:0005829 cytosol
IC
UniProtKB:C5CPT7 		NEW
Reason: Inferred by curator (IC) because PqqA (C5CPT7) is a 24-residue ribosomally translated precursor peptide lacking any signal peptide or transmembrane domain that undergoes initial PqqD-chaperoned, PqqE-catalyzed Glu16-Tyr20 cross-linking in the bacterial cytosol.
Supporting Evidence:
UniProtKB:C5CPT7
FT CROSSLNK 16..20 FT /note="Pyrroloquinoline quinone (Glu-Tyr)" FT /evidence="ECO:0000255|HAMAP-Rule:MF_00656"

Core Functions

Ribosomally synthesized 24-residue precursor peptide that supplies the conserved Glu16 and Tyr20 side chains for PqqD/PqqE-mediated carbon-carbon cross-linking and subsequent proteolytic and oxidative maturation into pyrroloquinoline quinone (PQQ); acts as a biosynthetic precursor scaffold rather than a catalytic enzyme.

Directly Involved In:
pyrroloquinoline quinone biosynthetic process
Cellular Locations:
cytosol
Supporting Evidence:
  • UniProtKB:C5CPT7
    CC -!- FUNCTION: Required for coenzyme pyrroloquinoline quinone (PQQ) CC biosynthesis. PQQ is probably formed by cross-linking a specific CC glutamate to a specific tyrosine residue and excising these residues CC from the peptide. {ECO:0000255|HAMAP-Rule:MF_00656}.
  • PMID:25817994
    Pyrroloquinoline quinone (PQQ) is a product of a ribosomally synthesized and post-translationally modified pathway consisting of five conserved genes, pqqA-E. PqqE is a radical S-adenosylmethionine (RS) protein with a C-terminal SPASM domain, and is proposed to catalyze the formation of a carbon-carbon bond between the glutamate and tyrosine side chains of the peptide substrate PqqA.

References

Loading supporting content…

Download this section (compressed HTML)

Suggested Questions for Experts

Q: Which cellular peptidase(s) in Variovorax paradoxus excise the Glu16-Tyr20 cross-linked dipeptide intermediate from Vapar_3057 (PqqA) following PqqE-catalyzed carbon-carbon bond formation?

Suggested Experiments

Experiment: Reconstitute Variovorax paradoxus PqqA (C5CPT7) with purified PqqD and PqqE in vitro and substitute Glu16 or Tyr20 by site-directed mutagenesis to verify loss of SAM-dependent intramolecular Glu-Tyr cross-linking by LC-HRMS/MS.

Hypothesis: Substitution of either Glu16 or Tyr20 in Vapar_3057 abolishes PqqE-catalyzed intramolecular C-C cross-link formation while preserving N-terminal leader peptide binding to PqqD.

Type: In vitro RiPP reconstitution and LC-HRMS/MS peptide mapping

📚 Additional Documentation

Notes

(pqqA-notes.md)

Loading supporting content…

Download this section (compressed HTML)

📄 View Raw YAML

Loading supporting content…

Download this section (compressed HTML)