XdhA is the FAD- and [2Fe-2S]-binding electron-transfer subunit of the two-subunit XdhAB xanthine dehydrogenase. XdhA relays electrons from the XdhB molybdenum catalytic subunit toward the terminal acceptor and contributes, with XdhB, to oxidation of hypoxanthine to xanthine and xanthine to urate. The KT2440 complex has not been characterized directly; the reaction assignment rests on subunit-specific domain architecture and homologous bacterial XDHs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004854 xanthine dehydrogenase activity | IEA GO_REF:0000120 | MODIFY | Summary: XdhA contributes the FAD/[2Fe-2S] electron-transfer module of XdhAB but does not catalyze the complete xanthine reaction alone. Reason: The term is right for the XdhAB complex, but the relation is not: replace the GOA enables relation with contributes_to (same term). Substrate oxidation occurs at the molybdenum center in XdhB, whereas XdhA supplies the electron-transfer arm of the assembled enzyme. The qualifier error is recorded as a source defect, and the intended contributes_to assertion is the paired NEW GO:0004854 row below. Proposed replacements: xanthine dehydrogenase activity Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR014307; Xanthine_DH_ssu. PMID:11341925 XDH from P. putida 86 consists of 91.0 kDa and 46.2 kDa file:PSEPK/xdhA/xdhA-deep-research-openscientist.md **XdhA's role is electron transfer** |
| GO:0005506 iron ion binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: XdhA binds iron only as part of its two [2Fe-2S] clusters, not as free iron ions. Reason: The row comes from the IPR016208 aldehyde oxidase/xanthine dehydrogenase superfamily mapping, which spans both subunits and the fused eukaryotic enzymes. XdhA's iron is bound only within its two [2Fe-2S] clusters; iron-sulfur cluster binding is not a descendant of iron ion binding in GO, and GO:0051537 is the accurate cofactor term for XdhA. Free iron ion binding is therefore an over-annotation. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR016208; Ald_Oxase/xanthine_DH-like. PMID:11341925 Resonances from FeSI and FeSII were detected at 15 K. |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: XdhA is a redox-active FAD/[2Fe-2S] subunit, but the oxidoreductase reactions are carried out by the XdhAB complex. Reason: The cited evidence places FAD and two iron-sulfur centers on the small subunit and shows that the molybdenum, FeSI and FAD potentials form a coupled relay, but no source shows XdhA catalysing an oxidoreduction on its own; the substrate oxidations need the XdhB molybdenum site. The enables relation to oxidoreductase activity therefore over-states the subunit's own function, which is captured by electron transfer activity and by contributes_to the two complete purine-base oxidations. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR002346; Mopterin_DH_FAD-bd. PMID:11341925 The midpoint potentials determined for the molybdenum, FeSI and FAD redox couples are close to each other |
| GO:0046872 metal ion binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: XdhA's metal content is the iron of its two [2Fe-2S] clusters. Reason: The row comes from the IPR002888 2Fe-2S-binding domain mapping. GO places 2 iron, 2 sulfur cluster binding under metal cluster binding, not under metal ion binding, so the generic metal-ion claim is not entailed by the specific cofactor row and overstates free metal-ion binding. GO:0051537 records the informative cofactor-binding class. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR002888; 2Fe-2S-bd. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but uninformative parent of the accepted GO:0071949 FAD binding row. Reason: GO:0071949 FAD binding is_a GO:0050660 flavin adenine dinucleotide binding, and the specific child is accepted on another row of this review, so this broad term is true but adds nothing. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR036318; FAD-bd_PCMH-like_sf. PMID:11341925 electron paramagnetic resonance (EPR) signals of the neutral FAD |
| GO:0051536 iron-sulfur cluster binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but uninformative parent of the accepted GO:0051537 [2Fe-2S] cluster binding row. Reason: GO:0051537 2 iron, 2 sulfur cluster binding is_a GO:0051536 iron-sulfur cluster binding, and the specific child is accepted on another row of this review, so this broad term is true but adds nothing. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type. PMID:11341925 Resonances from FeSI and FeSII were detected at 15 K. |
| GO:0051537 2 iron, 2 sulfur cluster binding | IEA GO_REF:0000002 | ACCEPT | Summary: XdhA contains the canonical bacterial XDH small-subunit [2Fe-2S]-binding architecture. Reason: Multiple ferredoxin-type and [2Fe-2S]-binding InterPro signatures support this specific cofactor annotation. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR006058; 2Fe2S_fd_BS. PMID:11341925 Resonances from FeSI and FeSII were detected at 15 K. |
| GO:0071949 FAD binding | IEA GO_REF:0000002 | ACCEPT | Summary: XdhA contains the FAD-binding module of bacterial xanthine dehydrogenase. Reason: The PCMH-type FAD-binding and xanthine-dehydrogenase small-subunit signatures support specific FAD binding. Supporting Evidence: file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR002346; Mopterin_DH_FAD-bd. PMID:11341925 electron paramagnetic resonance (EPR) signals of the neutral FAD |
| GO:0004854 xanthine dehydrogenase activity | ISS | NEW | Summary: XdhA contributes its FAD/[2Fe-2S] electron-transfer module to XdhAB oxidation of xanthine to urate. Reason: Relation-only partner of the GOA enables row above. The characterized P. putida strain-86 XDH oxidizes xanthine, and XdhA's architecture identifies it as the small subunit of the corresponding two-subunit enzyme. Supporting Evidence: PMID:11341925 oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using PMID:11341925 XDH from P. putida 86 consists of 91.0 kDa and 46.2 kDa file:PSEPK/xdhA/xdhA-uniprot.txt DR NCBIfam; TIGR02963; xanthine_xdhA; 1. |
| GO:0009055 electron transfer activity | ISS | NEW | Summary: XdhA supplies the FAD/[2Fe-2S] electron relay of the two-subunit XDH. Reason: This captures XdhA's independent subunit-level function without assigning complete substrate catalysis to XdhA alone. Supporting Evidence: PMID:11341925 The midpoint potentials determined for the molybdenum, FeSI and FAD redox couples are close to each other file:PSEPK/xdhA/xdhA-uniprot.txt DR InterPro; IPR014307; Xanthine_DH_ssu. |
| GO:0070674 hypoxanthine dehydrogenase activity | ISS | NEW | Summary: XdhA contributes its electron-transfer module to XdhAB oxidation of hypoxanthine to xanthine. Reason: The characterized P. putida strain-86 homolog oxidizes hypoxanthine, while XdhA's architecture identifies it as one subunit of the corresponding enzyme. Supporting Evidence: PMID:11341925 oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using file:PSEPK/xdhA/xdhA-uniprot.txt DR NCBIfam; TIGR02963; xanthine_xdhA; 1. |
| GO:0009114 hypoxanthine catabolic process | ISS | NEW | Summary: XdhAB converts hypoxanthine to xanthine, with XdhA providing the electron-transfer subunit. Reason: This is the immediate process for the first reaction attributed to the homologous two-subunit enzyme. Supporting Evidence: PMID:11341925 oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using |
| GO:0009115 xanthine catabolic process | ISS | NEW | Summary: XdhAB converts xanthine to urate, with XdhA providing the electron-transfer subunit. Reason: Xanthine oxidation is the defining substrate reaction of the homologous P. putida strain-86 XDH. Supporting Evidence: PMID:11341925 oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using |
| GO:0034418 urate biosynthetic process | ISS | NEW | Summary: The second XdhAB oxidation step produces urate from xanthine. Reason: Urate is the direct product of xanthine dehydrogenase activity, although this assignment remains inferred for the KT2440 complex. Supporting Evidence: PMID:11341925 oxidation of hypoxanthine, xanthine, purine, and some aromatic aldehydes, using |
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Download this section (compressed HTML)Q: Does the KT2440 XdhAB complex oxidize both hypoxanthine and xanthine with NAD+ as its preferred electron acceptor?
Suggested experts: bacterial molybdenum-enzyme experts
Experiment: Coexpress XdhA, XdhB, and the candidate maturation factor, purify the mature KT2440 complex, and measure hypoxanthine- and xanthine-dependent reduction of NAD+ alongside alternative electron acceptors.
Type: enzyme reconstitution assay
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