PA0317 encodes the bacterial D-2-hydroxyglutarate dehydrogenase (D2HGDH) of Pseudomonas aeruginosa PAO1, a 464-residue FAD-dependent oxidoreductase of the FAD-binding PCMH/type-4 oxidoreductase family. It catalyses the oxidation of (R)-2-hydroxyglutarate (D-2-HG) back to 2-oxoglutarate, passing electrons through electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase to the respiratory chain. The enzyme is functionally coupled to the L-serine biosynthetic pathway: SerA (D-3-phosphoglycerate dehydrogenase) produces D-2-HG while reducing 2-oxoglutarate as it oxidises 3-phosphoglycerate, and D2HGDH removes the D-2-HG, maintaining its homeostasis and pulling the thermodynamically unfavourable SerA reaction forward.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO catalytic activity from the FAD-oxidoreductase signatures. Reason: Entailed by the accepted GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity, which is_a catalytic activity. |
| GO:0006564 L-serine biosynthetic process | IMP PMID:28827360 Coupling between d-3-phosphoglycerate dehydrogenase and d-2-... | ACCEPT | Summary: PseudoCAP row. D2HGDH is coupled to SerA: it removes the D-2-HG produced during SerA's reduction of 2-oxoglutarate, and the deletion growth defect is rescued by L-serine, so the enzyme contributes to L-serine biosynthesis. Reason: The enzyme performs part of the serine-biosynthesis coupling (D-2-HG removal that pulls the SerA reaction forward), not merely a downstream phenotype. Supporting Evidence: PMID:28827360 the defect was rescued by adding l-serine, suggesting that the D2HGDH is |
| GO:0022904 respiratory electron transport chain | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA from PTN000202405 (a separate node, seeded by E. coli P06149 / succinate dehydrogenase-like flavoprotein) asserting respiratory electron transport chain. D2HGDH does feed electrons into the ETF/ubiquinone respiratory route. Reason: Consistent with the enzyme passing electrons to the respiratory chain via ETF/ETFQO, but peripheral to its core D-2-HG-oxidising role. Supporting Evidence: PMID:28827360 and ETF-ubiquinone oxidoreductase (ETFQO) are also essential in d-2-HG |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO FAD binding from the FAD-binding PCMH signatures. D2HGDH is an FAD-dependent enzyme. Reason: Correct cofactor binding, supported by the family assignment and the experimental identification of an FAD-dependent enzyme. Supporting Evidence: PMID:28827360 a flavin adenine dinucleotide (FAD)-dependent |
| GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC 1.1.99.39 / ARBA mapping of the (R)-2-hydroxyglutarate dehydrogenase activity, agreeing with the experimental IMP row. Reason: Consistent with the demonstrated activity. |
| GO:0051990 (R)-2-hydroxyglutarate dehydrogenase activity | IMP PMID:28827360 Coupling between d-3-phosphoglycerate dehydrogenase and d-2-... | ACCEPT | Summary: PseudoCAP row and the seed of the PTN005178867 D2HGDH IBD. Zhang et al. identified the bacterial FAD-dependent D-2-HG dehydrogenase in P. stutzeri A1501 and PAO1 and showed the deletion phenotype is rescued by L-serine. The activity was demonstrated biochemically, not merely inferred from a phenotype. Reason: Sound seed; this is the enzyme's own catalytic activity and core function. Supporting Evidence: PMID:28827360 d-2-HG dehydrogenase (D2HGDH), a flavin adenine dinucleotide (FAD)-dependent |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO FAD binding (GO:0071949) from a further FAD-binding signature; a sibling/descendant of the GO:0050660 term. Reason: Correct cofactor binding for this FAD enzyme. Supporting Evidence: PMID:28827360 a flavin adenine dinucleotide (FAD)-dependent |
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Download this section (compressed HTML)Q: Does PA0317 oxidise other D-2-hydroxy acids, or is it specific for D-2-HG as its coupling to SerA in L-serine synthesis implies?
Experiment: Steady-state kinetics of purified PA0317 with D-2-HG and candidate alternative substrates, with ETF as electron acceptor, to confirm substrate specificity and the physiological electron route.
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