Q7VZI5 (ordered locus BP0922) is an uncharacterised 391-residue protein of Bordetella pertussis in the PrpF/DUF453 family (PANTHER PTHR43709, subfamily SF2; Pfam PF04303; InterPro IPR007400). This family adopts the cofactor-independent, two-domain diaminopimelate epimerase (DapF) fold. Its characterised members isomerise unsaturated organic acids: the PrpF methylaconitate cis-trans/positional isomerase of the AcnD-dependent 2-methylcitrate cycle, the 3-methylitaconate delta-isomerase Mii, the fungal aconitate delta-isomerase Adi1, and the oxalomesaconate delta-isomerase and tautomerase enzymes LigU and GalD. Q7VZI5 conserves the catalytic lysine/cysteine pair that these enzymes share, so it is probably a soluble cytoplasmic isomerase of this kind. It is only about 36% identical to the PrpF enzymes, lacks the PrpF-specific TIGR02334 signature, and is encoded outside the B. pertussis prp (methylcitrate cycle) gene cluster, which has its own PrpF (BP2370). Its neighbours instead include an MmgE/PrpD-family protein, a succinate-semialdehyde dehydrogenase and a tricarboxylate-transport-like protein. The physiological substrate and pathway are unknown. Q7VZI5 is about equally related (35-45% identity) to characterised members with different substrates, so sequence similarity does not assign a specific reaction.
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Summary: This annotation is not in GOA. Q7VZI5 has no hydrophobic N-terminal signal sequence and no transmembrane-length hydrophobic segment (maximum Kyte-Doolittle 19-residue mean 1.52 overall and 0.55 in the first 40 residues). Characterised members of the family, such as S. oneidensis PrpF, are soluble intracellular enzymes.
Reason: Cytoplasm is a reasonable location for a soluble, cofactor-independent family isomerase that has no export or membrane signals. Confidence is modest, because the hydropathy screen is crude and there is no direct localisation data.
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Summary: Every characterised member of PTHR43709 is a cofactor-independent isomerase of the DapF fold. They include PrpF (methylaconitate/aconitate cis-trans isomerase), Mii (3-methylitaconate delta-isomerase), Adi1 (aconitate delta-isomerase), LigU (oxalomesaconate delta-isomerase) and GalD (oxalomesaconate tautomerase). Q7VZI5 keeps the proposed catalytic residues, Lys65 and Cys99, which correspond to PrpF Lys73 and Cys107.
Reason: Isomerase activity is the most specific function shared by all characterised members of the family, and Q7VZI5 retains the catalytic residues. The family includes both C=C-transposing delta-isomerases and a keto-enol tautomerase. Q7VZI5 has no close characterised neighbour, so no narrower class (GO:0016863 or GO:0016862) or substrate-specific child is warranted. The PAINT IBD for GO:0016863 is seeded by Shewanella PrpF, and Q7VZI5 has not inherited it.
The proposed catalytic Lys/Cys pair is conserved across the family, Q7VZI5 included.
Core Functions
Predicted cofactor-independent isomerase of the PrpF/DapF-fold family, acting on an unidentified unsaturated organic-acid substrate in the cytoplasm. Its physiological pathway is unknown and is distinct from the methylcitrate-cycle role of the B. pertussis PrpF paralog BP2370.
Q: What is the substrate of BP0922? The gene is paired with an MmgE/PrpD-family dehydratase (BP0918) in the same cluster. Does this pair form an AcnD/PrpF-like dehydratase-isomerase module for another tricarboxylic or methyl-branched acid, such as an alternative methylaconitate, homoaconitate-like or itaconate-derived substrate?
Q: Does a phylogeny of PTHR43709:SF2 place BP0922 in a clade with Mii, with Adi1, with YraM, or in a separate clade? Does that clade include any characterised member?
Suggested Experiments
Experiment: Purify Q7VZI5 and screen candidate substrates by HPLC or NMR: cis- and trans-aconitate, 2- and 4-methylaconitate isomers, itaconate and 3-methylitaconate, and oxalomesaconate. Compare with K65A and C99A mutants.
Hypothesis: Recombinant Q7VZI5 isomerises a C6/C7 unsaturated tricarboxylic or dicarboxylic acid, and the activity depends on Lys65 and Cys99.
Type: in vitro enzyme assay
Experiment: Grow a B. pertussis or B. bronchiseptica deletion of the BP0922 ortholog on propionate and on candidate organic acids, alongside a prpF (BP2370 ortholog) deletion as comparator. Complement both mutants.
Hypothesis: BP0922 is needed for growth on a carbon source catabolised by the BP0918-BP0925 cluster, not for growth on propionate.
Type: microbial growth assay
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
ProtNLM2 made no predictions (GO or subcellular location) for PrpF family protein. The model returned only a protein name. This is an assessed absence. The gene has no GOA annotations, and the gene review supports only isomerase activity (GO:0016853) in the cytoplasm, transferred at family level from characterised PTHR43709 (PrpF/DUF453) members; the physiological substrate is unknown. The family-level name "PrpF family protein" is consistent with this. It does not assign the PrpF-specific methylaconitate isomerase reaction, which the review argues against because Q7VZI5 lacks the TIGR02334 signature and lies outside the prp gene cluster. A PubMed search for the locus tag BP0922 returned no papers, so there is no gene-specific evidence for a more specific term.