XDH_BLAAD
ID XDH_BLAAD Reviewed; 1405 AA.
AC R4ZGN4;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2013, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Xanthine dehydrogenase {ECO:0000305};
DE Short=XD {ECO:0000250|UniProtKB:P47989};
DE EC=1.17.1.4 {ECO:0000269|PubMed:23773263};
DE AltName: Full=Xanthine oxidoreductase {ECO:0000303|PubMed:25513995, ECO:0000312|EMBL:CCV20080.1};
DE Short=Axorp {ECO:0000303|PubMed:23773263, ECO:0000303|PubMed:25513995};
DE Short=XOR {ECO:0000303|PubMed:23773263};
GN Name=AXOR {ECO:0000303|PubMed:23773263, ECO:0000303|PubMed:25513995};
GN ORFNames=GNLVRS02_ARAD1D12518g {ECO:0000312|EMBL:CDP37481.1};
OS Blastobotrys adeninivorans (Yeast) (Arxula adeninivorans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Trichomonascaceae; Blastobotrys.
OX NCBI_TaxID=409370 {ECO:0000312|EMBL:CCV20080.1};
RN [1] {ECO:0000312|EMBL:CCV20080.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-6, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP SUBSTRATE SPECIFICITY, PATHWAY, SUBUNIT, SUBCELLULAR LOCATION, INDUCTION,
RP DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RC STRAIN=LS3 {ECO:0000312|EMBL:CCV20080.1};
RX PubMed=23773263; DOI=10.1111/jam.12284;
RA Jankowska D.A., Trautwein-Schult A., Cordes A., Hoferichter P., Klein C.,
RA Bode R., Baronian K., Kunze G.;
RT "Arxula adeninivorans xanthine oxidoreductase and its application in the
RT production of food with low purine content.";
RL J. Appl. Microbiol. 115:796-807(2013).
RN [2] {ECO:0000312|EMBL:CDP37481.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LS3 {ECO:0000312|EMBL:CDP37481.1};
RX PubMed=24834124; DOI=10.1186/1754-6834-7-66;
RA Kunze G., Gaillardin C., Czernicka M., Durrens P., Martin T., Boeer E.,
RA Gabaldon T., Cruz J.A., Talla E., Marck C., Goffeau A., Barbe V., Baret P.,
RA Baronian K., Beier S., Bleykasten C., Bode R., Casaregola S., Despons L.,
RA Fairhead C., Giersberg M., Gierski P.P., Haehnel U., Hartmann A.,
RA Jankowska D., Jubin C., Jung P., Lafontaine I., Leh-Louis V., Lemaire M.,
RA Marcet-Houben M., Mascher M., Morel G., Richard G.F., Riechen J.,
RA Sacerdot C., Sarkar A., Savel G., Schacherer J., Sherman D.J., Stein N.,
RA Straub M.L., Thierry A., Trautwein-Schult A., Vacherie B., Westhof E.,
RA Worch S., Dujon B., Souciet J.L., Wincker P., Scholz U., Neuveglise C.;
RT "The complete genome of Blastobotrys (Arxula) adeninivorans LS3 - a yeast
RT of biotechnological interest.";
RL Biotechnol. Biofuels 7:66-66(2014).
RN [3]
RP PATHWAY, SUBUNIT, INDUCTION, AND BIOTECHNOLOGY.
RX PubMed=25513995; DOI=10.4161/21655979.2014.991667;
RA Jankowska D.A., Trautwein-Schult A., Cordes A., Bode R., Baronian K.,
RA Kunze G.;
RT "A novel enzymatic approach in the production of food with low purine
RT content using Arxula adeninivorans endogenous and recombinant purine
RT degradative enzymes.";
RL Bioengineered 6:20-25(2015).
CC -!- FUNCTION: Key enzyme in purine degradation. Catalyzes the oxidation of
CC hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric
CC acid. Oxidizes xanthine, hypoxanthine and pterine at high rates. Can
CC also act on purine and guanine. {ECO:0000269|PubMed:23773263}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + hypoxanthine + NAD(+) = H(+) + NADH + xanthine;
CC Xref=Rhea:RHEA:24670, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17368, ChEBI:CHEBI:17712, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.17.1.4;
CC Evidence={ECO:0000269|PubMed:23773263};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) + xanthine = H(+) + NADH + urate;
CC Xref=Rhea:RHEA:16669, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17712, ChEBI:CHEBI:17775, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.17.1.4;
CC Evidence={ECO:0000269|PubMed:23773263};
CC -!- COFACTOR:
CC Name=Mo-molybdopterin; Xref=ChEBI:CHEBI:71302;
CC Evidence={ECO:0000250|UniProtKB:P47989};
CC Note=Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
CC {ECO:0000250|UniProtKB:P47989};
CC -!- COFACTOR:
CC Name=[2Fe-2S] cluster; Xref=ChEBI:CHEBI:190135;
CC Evidence={ECO:0000250|UniProtKB:P47989};
CC Note=Binds 2 [2Fe-2S] clusters. {ECO:0000250|UniProtKB:P47989};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:P47989};
CC -!- ACTIVITY REGULATION: Completely inhibited by allopurinol and
CC significantly inhibited by adenine. Inhibited by Fe(2+), Cd(2+) and
CC Zn(2+) and strongly inhibited by Cu(2+). Mg(2+) and Mo(2+) have no
CC effect on activity. {ECO:0000269|PubMed:23773263}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=72.8 uM for xanthine in pH 8.5 and at 43 degrees Celsius
CC {ECO:0000269|PubMed:23773263};
CC KM=50.8 uM for hypoxanthine in pH 8.5 and at 43 degrees Celsius
CC {ECO:0000269|PubMed:23773263};
CC KM=162.5 uM for NAD(+) in pH 8.5 and at 43 degrees Celsius
CC {ECO:0000269|PubMed:23773263};
CC KM=208.0 uM for purine in pH 8.5 and at 43 degrees Celsius
CC {ECO:0000269|PubMed:23773263};
CC pH dependence:
CC Optimum pH is 8.5 in glycine-NaOH. Optimum pH is between 7.5 and 9.5
CC in potassium phosphate, Tris-HCl and Tris-acetate.
CC {ECO:0000269|PubMed:23773263};
CC Temperature dependence:
CC Optimum temperature is 43 degrees Celsius. Quite stable as loses only
CC 5% of activity in 1 h at 30 degrees Celsius, 12% at 40 degrees
CC Celsius and 25% at 50 degrees Celsius. {ECO:0000269|PubMed:23773263};
CC -!- PATHWAY: Purine metabolism. {ECO:0000269|PubMed:23773263,
CC ECO:0000269|PubMed:25513995}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23773263,
CC ECO:0000269|PubMed:25513995}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23773263}.
CC -!- INDUCTION: Most efficiently by hypoxanthine. Twice the level of the
CC transcription increase compared with the level due to induction by
CC adenine, which exhibits 10-fold increase from non-induced
CC (PubMed:23773263, PubMed:25513995). Low levels induced by ammonium and
CC nitrate. 43 mmol/l ammonium or nitrate and 2.5 mmol/l adenine together
CC induce only 2- to 3-fold higher levels compared to non-induced level
CC (PubMed:23773263). {ECO:0000269|PubMed:23773263,
CC ECO:0000269|PubMed:25513995}.
CC -!- DISRUPTION PHENOTYPE: Exhibits less than 1% of the wild-type activity
CC towards xanthine and hypoxanthine under inducible conditions (2.5
CC mmol/l adenine). No activity after cultivation without inducer.
CC {ECO:0000269|PubMed:23773263}.
CC -!- BIOTECHNOLOGY: This enzyme can be used as a potential additive in the
CC production of low purine content food, which is recommended to people
CC suffering from hyperuricemia that can at worst lead to gout. When used
CC in conjunction with other enzymes of the purine degradation pathway,
CC uric acid concentration is significantly reduced.
CC {ECO:0000269|PubMed:23773263, ECO:0000269|PubMed:25513995}.
CC -!- SIMILARITY: Belongs to the xanthine dehydrogenase family.
CC {ECO:0000305}.
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DR EMBL; HF935016; CCV20080.1; -; Genomic_DNA.
DR EMBL; HG937694; CDP37481.1; -; Genomic_DNA.
DR AlphaFoldDB; R4ZGN4; -.
DR SMR; R4ZGN4; -.
DR PhylomeDB; R4ZGN4; -.
DR BRENDA; 1.17.3.2; 468.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0051537; F:2 iron, 2 sulfur cluster binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0043546; F:molybdopterin cofactor binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0004854; F:xanthine dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0071242; P:cellular response to ammonium ion; IEP:UniProtKB.
DR GO; GO:0071276; P:cellular response to cadmium ion; IDA:UniProtKB.
DR GO; GO:0071280; P:cellular response to copper ion; IDA:UniProtKB.
DR GO; GO:0071281; P:cellular response to iron ion; IDA:UniProtKB.
DR GO; GO:0071249; P:cellular response to nitrate; IEP:UniProtKB.
DR GO; GO:0071294; P:cellular response to zinc ion; IDA:UniProtKB.
DR GO; GO:0006147; P:guanine catabolic process; IDA:UniProtKB.
DR GO; GO:0009114; P:hypoxanthine catabolic process; IDA:UniProtKB.
DR GO; GO:0006145; P:purine nucleobase catabolic process; IDA:UniProtKB.
DR GO; GO:0009115; P:xanthine catabolic process; IDA:UniProtKB.
DR CDD; cd00207; fer2; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 3.30.43.10; -; 1.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR002888; 2Fe-2S-bd.
DR InterPro; IPR036884; 2Fe-2S-bd_dom_sf.
DR InterPro; IPR036010; 2Fe-2S_ferredoxin-like_sf.
DR InterPro; IPR001041; 2Fe-2S_ferredoxin-type.
DR InterPro; IPR006058; 2Fe2S_fd_BS.
DR InterPro; IPR000674; Ald_Oxase/Xan_DH_a/b.
DR InterPro; IPR036856; Ald_Oxase/Xan_DH_a/b_sf.
DR InterPro; IPR016208; Ald_Oxase/xanthine_DH.
DR InterPro; IPR008274; AldOxase/xan_DH_Mopterin-bd.
DR InterPro; IPR037165; AldOxase/xan_DH_Mopterin-bd_sf.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR005107; CO_DH_flav_C.
DR InterPro; IPR036683; CO_DH_flav_C_dom_sf.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016167; FAD-bd_PCMH_sub1.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR002346; Mopterin_DH_FAD-bd.
DR PANTHER; PTHR11908; PTHR11908; 1.
DR Pfam; PF01315; Ald_Xan_dh_C; 1.
DR Pfam; PF02738; Ald_Xan_dh_C2; 1.
DR Pfam; PF03450; CO_deh_flav_C; 1.
DR Pfam; PF00941; FAD_binding_5; 1.
DR Pfam; PF00111; Fer2; 1.
DR Pfam; PF01799; Fer2_2; 1.
DR PIRSF; PIRSF000127; Xanthine_DH; 1.
DR SMART; SM01008; Ald_Xan_dh_C; 1.
DR SMART; SM01092; CO_deh_flav_C; 1.
DR SUPFAM; SSF47741; SSF47741; 1.
DR SUPFAM; SSF54292; SSF54292; 1.
DR SUPFAM; SSF54665; SSF54665; 1.
DR SUPFAM; SSF55447; SSF55447; 1.
DR SUPFAM; SSF56003; SSF56003; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS00197; 2FE2S_FER_1; 1.
DR PROSITE; PS51085; 2FE2S_FER_2; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 1: Evidence at protein level;
KW 2Fe-2S; Cytoplasm; Direct protein sequencing; FAD; Flavoprotein; Iron;
KW Iron-sulfur; Metal-binding; Molybdenum; NAD; Oxidoreductase;
KW Purine metabolism.
FT CHAIN 1..1405
FT /note="Xanthine dehydrogenase"
FT /id="PRO_0000434943"
FT DOMAIN 17..104
FT /note="2Fe-2S ferredoxin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00465"
FT DOMAIN 288..474
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT ACT_SITE 1333
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 56
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47989,
FT ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 61
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47989,
FT ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 64
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47989,
FT ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 86
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P47989,
FT ECO:0000255|PROSITE-ProRule:PRU00465"
FT BINDING 125
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 128
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 161
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 163
FT /ligand="[2Fe-2S] cluster"
FT /ligand_id="ChEBI:CHEBI:190135"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 316..323
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 397
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 407..411
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 420
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 464
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 483
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 833
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 864
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 868
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 946
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 978
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P47989"
FT BINDING 980
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P80457"
FT BINDING 1147
FT /ligand="Mo-molybdopterin"
FT /ligand_id="ChEBI:CHEBI:71302"
FT /ligand_part="Mo"
FT /ligand_part_id="ChEBI:CHEBI:28685"
FT /evidence="ECO:0000250|UniProtKB:P47989"
SQ SEQUENCE 1405 AA; 153207 MW; F5F45168261FF1FD CRC64;
MVDLQLHQSL GHHNFTNKLT FYVNGVKRTI SNPDPRGTLL DFIRTHEGLT GTKLGCSEGG
CGACTVVVAS WDREQGEIIY SAVNSCIVPL VAVEGKHLIT VEGIGSSNNP HPAQERIALF
HGSQCGFCTP GIVMSLYALL RNTGGQPSKE QIAESFDGNL CRCTGYKPII DAANTFSCGR
PGGCCRDNAS GKANGAGATV GNGMANGAAA VANGNGAAAN GCCKGNGAAN GCCKSNGSAA
TTANGDDKEV DMNKLFTPNG LPLKPYSAKT ELIFPPALKK YELNPLFFGN EQKVWFRPVT
KLQLLQIKHA YPESKIVGGA SEIQIEIKMK AANYNISVYA NDIEELKTHK YIPGKGLEFG
ANISLSKLEE VCDKLVHELD PNVSQIYGAI LEQLKYFAGR QIRNAATPAG NIATASPISD
LNPVLVAAEA VLTVESIENG EEQISMTDFF VGYRKTKLPA HGVITKIFVP ETVPRNEVVM
AYKQAKRKDD DIAIVTACLR LALDDDFRIS KARLAYGGVG PFTTAAKGTA EFLTGKLLRR
ETAKEVLEGA IDCLIKEFDL PYSVPGGMAA YRRTLIMSFF YKFYSTVLEK IGLAGEAQDN
SALENTYDPQ ALLEVTRKHP VGSRDLTNPY EQRIVGKSDP HLSALKQVTG EAVYIDDIPP
YHGECFGVQV MSTKPRARIL SVDPSPALEV EGVVGYVDVN DLPSREANIW GPTPVGKEPF
FADGEVYYVG QCIGVIIATD RMIAEEAARL VKVEYEELET VITIEEAIEA QSFFDYQPKA
EKGDVDGAFA ESAYTFEGTS RIGSQEHFYL ETQGSLVVPE PEDGEMKVYS SSQNPTETQV
FVAQATGVPS SRIVARVKRL GGGFGGKESR CCHLSSIAAV AAKKYKRPVR MILSRSEDML
TAGQRHPFVM KWKVGLDKNY KFTALEAKLY ANAGWSMDLT KGVIERAVLH AENCYDFPNA
RIQGIPCRTS VASNTAFRGF GGPQGMFMAE CYIYEIADQL GIEPDTLREI NYLVPGVSST
PFKQAITEDF TVPDMVKQIK KQSNYDDLRR QVEEFNSKHK WIKRGLAHVP TMFGISFGAT
FLNQAGALVH IYHDGSILLT HGGTEMGQGL HTKMAMVCAE ELKVPLSQVF ISETSTNTVP
NTSASAASAS SDLNGMAVKH ACDQLNERLA PYRERLGENA TMEQLAHAAY FDRVNLSANG
FYKTPDIGFV WGDPNPKPAF FYFTQGCAVA MVEVNTLTGD WSNLRTDIVM DIGRPINQAI
DYGQIEGAFV QGQGLFTIEE SLWLRNGALF TRGPGAYKIP GFRDIPQEFN VGHLRDRPFK
HLKTIHRSKG IGEPPLFLGS SVFFAIRDAL SYARRQNLGE ATMPAGLVAP MTTERIRMLA
GDSLYEHKGK IEPTEGDDKP FFVNA
