T23O_DROME
ID T23O_DROME Reviewed; 379 AA.
AC P20351; Q9VZ50;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Tryptophan 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE Short=TDO {ECO:0000255|HAMAP-Rule:MF_03020};
DE EC=1.13.11.11 {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:23333332};
DE AltName: Full=Protein vermilion {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000303|PubMed:2108317};
DE AltName: Full=Tryptamin 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE AltName: Full=Tryptophan oxygenase {ECO:0000255|HAMAP-Rule:MF_03020};
DE Short=TO {ECO:0000255|HAMAP-Rule:MF_03020};
DE Short=TRPO {ECO:0000255|HAMAP-Rule:MF_03020};
DE AltName: Full=Tryptophan pyrrolase {ECO:0000255|HAMAP-Rule:MF_03020};
DE AltName: Full=Tryptophanase {ECO:0000255|HAMAP-Rule:MF_03020};
GN Name=v {ECO:0000255|HAMAP-Rule:MF_03020}; ORFNames=CG5163;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=2108317; DOI=10.1128/mcb.10.4.1423-1431.1990;
RA Searles L.L., Ruth R.S., Pret A.-M., Fridell R.A., Ali A.J.;
RT "Structure and transcription of the Drosophila melanogaster vermilion gene
RT and several mutant alleles.";
RL Mol. Cell. Biol. 10:1423-1431(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5] {ECO:0007744|PDB:4HKA}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 24-379 IN COMPLEX WITH HEME,
RP CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF ASP-123; TYR-236; ARG-309
RP AND TYR-335.
RX PubMed=23333332; DOI=10.1016/j.jsb.2013.01.002;
RA Huang W., Gong Z., Li J., Ding J.;
RT "Crystal structure of Drosophila melanogaster tryptophan 2,3-dioxygenase
RT reveals insights into substrate recognition and catalytic mechanism.";
RL J. Struct. Biol. 181:291-299(2013).
CC -!- FUNCTION: Heme-dependent dioxygenase that catalyzes the oxidative
CC cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-
CC tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage
CC of the indole moiety (PubMed:23333332). Required during larval growth
CC to control the level of potentially harmful free tryptophan in the
CC hemolymph. In the adult the same reaction is the first step in the
CC ommochrome biosynthetic pathway (PubMed:2108317). {ECO:0000255|HAMAP-
CC Rule:MF_03020, ECO:0000269|PubMed:23333332,
CC ECO:0000303|PubMed:2108317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tryptophan + O2 = N-formyl-L-kynurenine;
CC Xref=Rhea:RHEA:24536, ChEBI:CHEBI:15379, ChEBI:CHEBI:57912,
CC ChEBI:CHEBI:58629; EC=1.13.11.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03020, ECO:0000269|PubMed:23333332};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03020,
CC ECO:0000269|PubMed:23333332};
CC Note=Binds 1 heme group per subunit. {ECO:0000255|HAMAP-Rule:MF_03020,
CC ECO:0000269|PubMed:23333332};
CC -!- PATHWAY: Amino-acid degradation; L-tryptophan degradation via
CC kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.
CC {ECO:0000255|HAMAP-Rule:MF_03020, ECO:0000269|PubMed:23333332}.
CC -!- PATHWAY: Pigment biosynthesis; ommochrome biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03020}.
CC -!- SUBUNIT: Homotetramer. Dimer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_03020, ECO:0000269|PubMed:23333332}.
CC -!- DEVELOPMENTAL STAGE: High in late larvae and in adult.
CC {ECO:0000269|PubMed:2108317}.
CC -!- SIMILARITY: Belongs to the tryptophan 2,3-dioxygenase family.
CC {ECO:0000255|HAMAP-Rule:MF_03020}.
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DR EMBL; M34147; AAA29014.1; -; Genomic_DNA.
DR EMBL; AE014298; AAF47978.1; -; Genomic_DNA.
DR EMBL; AY051478; AAK92902.1; -; mRNA.
DR PIR; A34780; A34780.
DR RefSeq; NP_511113.1; NM_078558.3.
DR PDB; 4HKA; X-ray; 2.70 A; A=24-379.
DR PDBsum; 4HKA; -.
DR AlphaFoldDB; P20351; -.
DR SMR; P20351; -.
DR BioGRID; 58442; 2.
DR IntAct; P20351; 1.
DR STRING; 7227.FBpp0073242; -.
DR PaxDb; P20351; -.
DR DNASU; 32026; -.
DR EnsemblMetazoa; FBtr0073386; FBpp0073242; FBgn0003965.
DR GeneID; 32026; -.
DR KEGG; dme:Dmel_CG2155; -.
DR UCSC; CG2155-RA; d. melanogaster.
DR CTD; 32026; -.
DR FlyBase; FBgn0003965; v.
DR VEuPathDB; VectorBase:FBgn0003965; -.
DR eggNOG; KOG3906; Eukaryota.
DR HOGENOM; CLU_045599_1_1_1; -.
DR InParanoid; P20351; -.
DR OMA; WRWRNDH; -.
DR OrthoDB; 896211at2759; -.
DR PhylomeDB; P20351; -.
DR BRENDA; 1.13.11.11; 1994.
DR BRENDA; 1.13.11.52; 1994.
DR Reactome; R-DME-71240; Tryptophan catabolism.
DR UniPathway; UPA00271; -.
DR UniPathway; UPA00333; UER00453.
DR BioGRID-ORCS; 32026; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 32026; -.
DR PRO; PR:P20351; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0003965; Expressed in insect adult head and 11 other tissues.
DR ExpressionAtlas; P20351; baseline and differential.
DR Genevisible; P20351; DM.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004833; F:tryptophan 2,3-dioxygenase activity; IDA:UniProtKB.
DR GO; GO:0048072; P:compound eye pigmentation; TAS:FlyBase.
DR GO; GO:0070189; P:kynurenine metabolic process; IMP:FlyBase.
DR GO; GO:0006727; P:ommochrome biosynthetic process; IMP:FlyBase.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:FlyBase.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0006569; P:tryptophan catabolic process; TAS:FlyBase.
DR GO; GO:0019442; P:tryptophan catabolic process to acetyl-CoA; IBA:GO_Central.
DR GO; GO:0019441; P:tryptophan catabolic process to kynurenine; IDA:UniProtKB.
DR HAMAP; MF_01972; T23O; 1.
DR InterPro; IPR037217; Trp/Indoleamine_2_3_dOase-like.
DR InterPro; IPR004981; Trp_2_3_dOase.
DR PANTHER; PTHR10138; PTHR10138; 1.
DR Pfam; PF03301; Trp_dioxygenase; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Heme; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome; Tryptophan catabolism.
FT CHAIN 1..379
FT /note="Tryptophan 2,3-dioxygenase"
FT /id="PRO_0000065780"
FT BINDING 57..61
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT BINDING 312
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020,
FT ECO:0000269|PubMed:23333332, ECO:0007744|PDB:4HKA"
FT BINDING 327
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03020"
FT MUTAGEN 123
FT /note="D->A: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:23333332"
FT MUTAGEN 236
FT /note="Y->F: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:23333332"
FT MUTAGEN 309
FT /note="R->A: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:23333332"
FT MUTAGEN 335
FT /note="Y->F: Strongly reduced enzyme activity."
FT /evidence="ECO:0000269|PubMed:23333332"
FT HELIX 27..30
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 43..46
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 54..82
FT /evidence="ECO:0007829|PDB:4HKA"
FT STRAND 83..85
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 89..116
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 121..125
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 128..130
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 135..137
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 140..149
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 170..181
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:4HKA"
FT TURN 201..204
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 206..226
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 231..252
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 254..262
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 270..281
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 286..320
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 331..338
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 348..351
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 352..356
FT /evidence="ECO:0007829|PDB:4HKA"
FT HELIX 360..362
FT /evidence="ECO:0007829|PDB:4HKA"
SQ SEQUENCE 379 AA; 44421 MW; E9E4C1B1C86D687F CRC64;
MSCPYAGNGN DHDDSAVPLT TEVGKIYGEY LMLDKLLDAQ CMLSEEDKRP VHDEHLFIIT
HQAYELWFKQ IIFEFDSIRD MLDAEVIDET KTLEIVKRLN RVVLILKLLV DQVPILETMT
PLDFMDFRKY LAPASGFQSL QFRLIENKLG VLTEQRVRYN QKYSDVFSDE EARNSIRNSE
KDPSLLELVQ RWLERTPGLE ESGFNFWAKF QESVDRFLEA QVQSAMEEPV EKAKNYRLMD
IEKRREVYRS IFDPAVHDAL VRRGDRRFSH RALQGAIMIT FYRDEPRFSQ PHQLLTLLMD
IDSLITKWRY NHVIMVQRMI GSQQLGTGGS SGYQYLRSTL SDRYKVFLDL FNLSTFLIPR
EAIPPLDETI RKKLINKSV
