C8VSZ2 · XANA_EMENI
- ProteinAlpha-ketoglutarate-dependent xanthine dioxygenase xanA
- GenexanA
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids370 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Alpha-ketoglutarate-dependent xanthine dioxygenase is a non-heme mononuclear Fe2+ enzyme that decarboxylates alpha-ketoglutarate to succinate and CO2 while hydroxylating xanthine to generate uric acid (PubMed:15948966, PubMed:17429948, PubMed:18036331).
Allows xanthine utilization as a nitrogen source (PubMed:15948966).
Whereas xanA is highly specific for xanthine, alpha-ketoadipic acid can replace alpha-ketoglutarate as a cosubstrate (PubMed:17429948).
Exhibits ferroxidase activity in the absence of substrates (PubMed:18036331).
Allows xanthine utilization as a nitrogen source (PubMed:15948966).
Whereas xanA is highly specific for xanthine, alpha-ketoadipic acid can replace alpha-ketoglutarate as a cosubstrate (PubMed:17429948).
Exhibits ferroxidase activity in the absence of substrates (PubMed:18036331).
Catalytic activity
- xanthine + 2-oxoglutarate + O2 = urate + succinate + CO2This reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 Fe2+ ion per subunit.
Activity regulation
Cu2+ and Zn2+ completely inhibit the xanthine dioxygenase activity, whereas Co2+, Mn2+, and Ni2+ partially inhibit the activity. The inactive metal ions are presumed to compete for the Fe2+-binding site (PubMed:17429948).
N-oxalylglycine (NOG), a known inhibitor of several Fe2+/alpha-ketoglutarate-dependent dioxygenase family members, competes with alpha-ketoglutarate and provides a Ki of 0.12 uM for inhibition (PubMed:17429948).
6,8-dihydroxypurine acts as a slow-binding competitive inhibitor (PubMed:18036331).
The thiol-specific inhibitors 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and iodoacetamide, inhibit also the catalytic activity (PubMed:18036331).
N-oxalylglycine (NOG), a known inhibitor of several Fe2+/alpha-ketoglutarate-dependent dioxygenase family members, competes with alpha-ketoglutarate and provides a Ki of 0.12 uM for inhibition (PubMed:17429948).
6,8-dihydroxypurine acts as a slow-binding competitive inhibitor (PubMed:18036331).
The thiol-specific inhibitors 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and iodoacetamide, inhibit also the catalytic activity (PubMed:18036331).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
31.1 μM | 2-oxoglutarate | 25 | ||||
50 μM | 2-oxoglutarate | 30 | ||||
45.2 μM | xanthine | 25 | ||||
46 μM | xanthine | 30 | ||||
0.16 mM | alpha-ketoadipic acid | 25 | ||||
0.4 mM | 9-methylxanthine | 25 |
pH Dependence
Optimum pH is 6.5 to 7.4.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 107 | substrate | ||||
Sequence: H | ||||||
Binding site | 149 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 151 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 195 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 325 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 340 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 352 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | alpha-ketoglutarate-dependent xanthine dioxygenase activity | |
Molecular Function | metal ion binding |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAlpha-ketoglutarate-dependent xanthine dioxygenase xanA
- EC number
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Aspergillus > Aspergillus subgen. Nidulantes
Accessions
- Primary accessionC8VSZ2
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 101 | Leads to elevated ferroxidase activity in the absence of substrates. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 122 | Affects the binding of 2-oxoglutarate. | ||||
Sequence: K → A | ||||||
Mutagenesis | 137 | Exhibits relatively enhanced activity and affects the inhibition by 6,8-dihydroxypurine. | ||||
Sequence: E → A | ||||||
Mutagenesis | 138 | Exhibits relatively enhanced activity and affects the inhibition by 6,8-dihydroxypurine. | ||||
Sequence: D → A | ||||||
Mutagenesis | 149 | Impairs catalytic activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 151 | Impairs catalytic activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 167 | In xanA1; impairs catalytic activity. | ||||
Sequence: A → D | ||||||
Mutagenesis | 340 | Exhibits only 0.17% of the wild-type enzyme activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 356 | Leads to elevated ferroxidase activity in the absence of substrates and affects the inhibition by 6,8-dihydroxypurine. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 357 | Exhibits relatively enhanced activity, resistance to thiol-specific inhibitors such as DTNB or iodoacetamide, and elevated ferroxidase activity in the absence of substrates. | ||||
Sequence: C → A | ||||||
Mutagenesis | 358 | Exhibits a 23-fold decrease in kcat/Km and affects the inhibition by 6,8-dihydroxypurine. | ||||
Sequence: N → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000446005 | 1-370 | Alpha-ketoglutarate-dependent xanthine dioxygenase xanA | |||
Sequence: MPAITVKPLTPPAGSAIDFGAVITDVDLEHLTDGDFSTIRSALYTHLVVVLKNQHQLTPKAQYELTRRFDPSATQYGHGKTLDAKRSILHPDLKTIPHQPQVQVIGHGFIDSYEGLENITLKHPHHRTFHRDPIPQEDDYDSTRFYRWHIDAALYGLNPPIVTTLLAVKVPGGRRQTVRYDDGSGETMDVPLGTTAFASGERMFELLSEEDKEFALSSRVEYAPHPYIWMSPARSLPTGLGLHSDDLELPLSELPPIDESAIQILPMVWKNPATGKPALQIHPSAVRKIHCGDGTVIDDLKKVREIAYKLQRPAISPQYVYAHDWEEGDLVLFHNRGVLHSVVGAFGEGEVRLFRQCNLAAGEGVVPYRE |
Post-translational modification
Phosphorylated.
Interaction
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length370
- Mass (Da)41,305
- Last updated2019-01-16 v2
- Checksum5E3A746FDBFAC33A
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AACD01000007 EMBL· GenBank· DDBJ | EAA66587.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
BN001308 EMBL· GenBank· DDBJ | CBF89386.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. |