Curation Notes for Variovorax paradoxus pqqD (A0A0H2M992, VPARA_00930)
Overview
- UniProt Accession:
A0A0H2M992 (A0A0H2M992_VARPD)
- Ordered Locus Name:
VPARA_00930 (encoded between pqqC [VPARA_00940] and pqqE [VPARA_00920] in the pqqBCDE cluster)
- Gene Symbol:
pqqD
- Organism: Variovorax paradoxus (
NCBITaxon:34073, strain TBEA6)
- Protein Function: 98-amino-acid cofactor-less PqqA-binding peptide chaperone (
PqqD, prototype of the RiPP recognition element [RRE] domain; HAMAP-Rule:MF_00655, InterPro:IPR008792, InterPro:IPR022479, NCBIfam:TIGR03859, Pfam:PF05402) in pyrroloquinoline quinone (PQQ) biosynthesis (UniProtKB:A0A0H2M992).
Removal of False-Positive GO:0048038 (quinone binding) Annotation
InterPro:IPR022479 (PqqD_bac) maps A0A0H2M992 to GO:0048038 (quinone binding) via GO_REF:0000002.- This is a well-documented InterPro2GO error (also removed in
PSEPK/pqqD1): PqqD does not bind mature PQQ or any quinone cofactor. As demonstrated by Latham et al. 2015 ([PMID:25817994 PqqD is a novel peptide chaperone that forms a ternary complex with the radical S-adenosylmethionine protein PqqE in the pyrroloquinoline quinone biosynthetic pathway., "Moreover, using SPR and isothermal calorimetry techniques, we establish for the first time that MePqqD binds MePqqA tightly (KD ∼200 nm)."]), Barr et al. 2016 ([PMID:26961875 Demonstration That the Radical S-Adenosylmethionine (SAM) Enzyme PqqE Catalyzes de Novo Carbon-Carbon Cross-linking within a Peptide Substrate PqqA in the Presence of the Peptide Chaperone PqqD., "These results indicate that PqqE, in conjunction with PqqD, carries out the first step in PQQ biosynthesis"]), and Zhu & Klinman 2020 ([PMID:32731194 Biogenesis of the peptide-derived redox cofactor pyrroloquinoline quinone., "The missing factor has turned out to be PqqD, a small, cofactor-less protein that primarily exists as a free protein (and occasionally as a C-terminal fusion protein of PqqC or an N-terminal fusion of PqqE) (Figure 1D).[12]"]), PqqD is a cofactor-less peptide chaperone that binds the unmodified precursor peptide PqqA (GO:0042277 peptide binding) and presents it to PqqE in a 1:1:1 ternary complex.
- Pathway context is modeled in
MODULE:pqq_biosynthesis.
Review of Existing GOA Annotations
GO:0018189 (pyrroloquinoline quinone biosynthetic process, IEA via UniProtKB-UniRule:UR000098302) -> ACCEPT (core biological process).GO:0048038 (quinone binding, IEA via InterPro:IPR022479) -> REMOVE (false-positive InterPro2GO mapping; PqqD is a cofactor-less peptide-binding chaperone for PqqA, not a quinone-binding protein).
New Annotations Added
GO:0042277 (peptide binding, ISS from PMID:25817994) — binds the precursor peptide PqqA (Kd ~ 200 nM).GO:0005829 (cytosol, IC, located_in) — soluble 98-residue cytosolic monomer that forms the PqqA-PqqD-PqqE complex.