Curation Notes for Variovorax paradoxus pqqB (A0A0H2M8Q2, VPARA_00950)
Overview
- UniProt Accession:
A0A0H2M8Q2 (A0A0H2M8Q2_VARPD)
- Ordered Locus Name:
VPARA_00950 (pqqB1 / pqqB, encoded at the 5' end of the pqqBCDE cluster VPARA_00950–VPARA_00920)
- Gene Symbol:
pqqB
- Organism: Variovorax paradoxus (
NCBITaxon:34073, strain TBEA6)
- Protein Function: 307-amino-acid metallo-$\beta$-lactamase-fold (
FT DOMAIN 53..274, Pfam:PF12706, InterPro:IPR011842, NCBIfam:TIGR02108, PANTHER:PTHR42663:SF7) non-heme $\text{Fe}^{2+}$-dependent hydroxylase in pyrroloquinoline quinone (PQQ) biosynthesis (UniProtKB:A0A0H2M8Q2).
Resolution of Historical UniProt/HAMAP Annotation Defect
UniProtKB:A0A0H2M8Q2 (HAMAP-Rule:MF_00653) still carries the legacy comment CC -!- FUNCTION: May be involved in the transport of PQQ or its precursor to the periplasm. and keyword KW Transport.- However, biochemical, $^{18}\text{O}_2$-labeling, and crystallographic characterization by Koehn et al. 2019 ([PMID:30811189 Discovery of Hydroxylase Activity for PqqB Provides a Missing Link in the Pyrroloquinoline Quinone Biosynthetic Pathway., "Here we show evidence that the remaining essential biosynthetic enzyme PqqB is an iron-dependent hydroxylase catalyzing oxygen-insertion reactions that are proposed to produce the quinone moiety of the mature PQQ cofactor."]) and reviewed by Zhu & Klinman 2020 ([PMID:32731194 Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone., "Detailed kinetic analyses have confirmed that PqqB is a previously unknown iron-dependent hydroxylase, indicating a cross-over between the MBL superfamily and the non-heme iron hydroxylases."]) established that PqqB is a cytosolic non-heme iron-dependent hydroxylase that oxygenates the tyrosine ring of a PqqA-derived cross-linked intermediate to form the hydroxyquinone precursor that cyclizes to AHQQ.
- Sequence inspection of
A0A0H2M8Q2 confirms both the N-terminal structural $\text{Zn}^{2+}$-binding motif (Cys19-Asn20-Cys21-Pro22-Asn23-Cys24, i.e. Cys19-X-Cys21-X2-Cys24 in 17-WNCNCPNC-24) and the metallo-$\beta$-lactamase fold (residues 53–274).
- Pathway context is modeled in
MODULE:pqq_biosynthesis.
Review of Existing GOA Annotations
GO:0018189 (pyrroloquinoline quinone biosynthetic process, IEA via UniProtKB-UniRule:UR000098300) -> ACCEPT (core biological process).
New Annotations Added
GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, ISS from PMID:30811189) — matches PSEPK/pqqB and MODULE:pqq_biosynthesis (pqqb_hydroxylase).GO:0005506 (iron ion binding, ISS from PMID:30811189) — catalytic $\text{Fe}^{2+}$ cofactor required for PqqB hydroxylase activity.GO:0005829 (cytosol, IC, located_in) — soluble 307-residue cytoplasmic enzyme lacking signal peptides or transmembrane helices.