PP_2325 encodes a soluble ApbA-fold NAD(P)-dependent oxidoreductase related to ketopantoate reductases. Q88KG5 belongs to a KPR-related PANTHER subfamily distinct from the canonical PanE family. Its reciprocal-best Pseudomonas aeruginosa ortholog, PaKPR2, has evolved broad alpha-keto-acid reductase activity and is inactive toward ketopantoate, so the native substrate of the KT2440 protein remains unresolved.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000118 | ACCEPT | Summary: Cytoplasmic localization is consistent with this soluble oxidoreductase. Reason: Q88KG5 has a soluble Rossmann-like/ApbA architecture and no signal peptide or transmembrane segment. Supporting Evidence: file:PSEPK/PP_2325/PP_2325-uniprot.txt DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. |
| GO:0008677 2-dehydropantoate 2-reductase activity | IEA GO_REF:0000120 | REMOVE | Summary: The substrate-specific KPR assignment is not supported for this paralog. Reason: The annotation is an electronic EC/rule transfer within a functionally heterogeneous KPR-related family. PP_2325 is the reciprocal-best-BLAST KT2440 ortholog of P. aeruginosa PaKPR2, which was structurally and biochemically shown to be inactive toward ketopantoate and active on other alpha-keto acids. This supports a broad oxidoreductase role but argues against retaining the specific ketopantoate reaction. Supporting Evidence: file:PSEPK/PP_2325/PP_2325-uniprot.txt DR InterPro; IPR051402; KPR-Related. file:PSEPK/PP_2325/PP_2325-notes.md OrtholugeDB identifies PP_2325 as the reciprocal-best-BLAST ortholog of PA1752 PMID:38962820 resulting in its inactivity toward the natural substrate ketopantoate |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | ISS PMID:38962820 Implication of Molecular Constraints Facilitating the Functi... | NEW | Summary: This donor and cofactor class captures the supported family-level function without asserting a substrate. Reason: Q88KG5 has an NAD(P)-binding ApbA oxidoreductase architecture and is the close Pseudomonas ortholog of an experimentally characterized broad alpha-keto-acid reductase. GO:0016616 captures the alcohol/oxo-acid redox chemistry and NAD(P) cofactor class without asserting a native substrate. Supporting Evidence: file:PSEPK/PP_2325/PP_2325-uniprot.txt DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. file:PSEPK/PP_2325/PP_2325-notes.md KPR-related alpha-keto-acid oxidoreductase of unresolved native substrate PMID:38962820 active against several important Ξ±-keto-acid substrates |
| GO:0015940 pantothenate biosynthetic process | IEA GO_REF:0000120 | REMOVE | Summary: Pantothenate-pathway placement is an electronic consequence of the unsupported KPR reaction. Reason: UniPathway placement depends on the EC 1.1.1.169 assignment. The close experimentally characterized ortholog does not reduce ketopantoate, and canonical panE/PP_1351 already supplies the pathway reaction in KT2440. Supporting Evidence: file:PSEPK/PP_2325/PP_2325-notes.md remove the specific ketopantoate/pantothenate assertions file:projects/P_PUTIDA/deep-research/PSEPK__coenzyme_a_biosynthesis__ppu00770-deep-research-openscientist.md The key curation question is which paralog is the physiologic flux carrier |
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Experiment: Purify Q88KG5 and compare reduction of ketopantoate with the alpha-keto-acid panel used for PaKPR2, then test the strongest substrates in targeted KT2440 deletion and metabolomics experiments.
Type: biochemical and genetic analysis
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