T23O_CUPMC
ID T23O_CUPMC Reviewed; 299 AA.
AC Q1LK00;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Tryptophan 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_01972};
DE Short=TDO {ECO:0000255|HAMAP-Rule:MF_01972};
DE EC=1.13.11.11 {ECO:0000255|HAMAP-Rule:MF_01972};
DE AltName: Full=Tryptamin 2,3-dioxygenase {ECO:0000255|HAMAP-Rule:MF_01972};
DE AltName: Full=Tryptophan oxygenase {ECO:0000255|HAMAP-Rule:MF_01972};
DE Short=TO {ECO:0000255|HAMAP-Rule:MF_01972};
DE Short=TRPO {ECO:0000255|HAMAP-Rule:MF_01972};
DE AltName: Full=Tryptophan pyrrolase {ECO:0000255|HAMAP-Rule:MF_01972};
DE AltName: Full=Tryptophanase {ECO:0000255|HAMAP-Rule:MF_01972};
GN Name=kynA {ECO:0000255|HAMAP-Rule:MF_01972}; OrderedLocusNames=Rmet_2651;
OS Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 /
OS CH34) (Ralstonia metallidurans).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Cupriavidus.
OX NCBI_TaxID=266264;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43123 / DSM 2839 / NBRC 102507 / CH34;
RX PubMed=20463976; DOI=10.1371/journal.pone.0010433;
RA Janssen P.J., Van Houdt R., Moors H., Monsieurs P., Morin N., Michaux A.,
RA Benotmane M.A., Leys N., Vallaeys T., Lapidus A., Monchy S., Medigue C.,
RA Taghavi S., McCorkle S., Dunn J., van der Lelie D., Mergeay M.;
RT "The complete genome sequence of Cupriavidus metallidurans strain CH34, a
RT master survivalist in harsh and anthropogenic environments.";
RL PLoS ONE 5:E10433-E10433(2010).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14700627; DOI=10.1016/j.chembiol.2003.11.011;
RA Kurnasov O., Goral V., Colabroy K., Gerdes S., Anantha S., Osterman A.,
RA Begley T.P.;
RT "NAD biosynthesis: identification of the tryptophan to quinolinate pathway
RT in bacteria.";
RL Chem. Biol. 10:1195-1204(2003).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 19-299 IN COMPLEX WITH HEME,
RP FUNCTION, CATALYTIC ACTIVITY, HOMOTETRAMERIZATION, AND MUTAGENESIS OF
RP PHE-68; TYR-130; ARG-134 AND THR-271.
RX PubMed=17198384; DOI=10.1021/bi0620095;
RA Zhang Y., Kang S.A., Mukherjee T., Bale S., Crane B.R., Begley T.P.,
RA Ealick S.E.;
RT "Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme
RT enzyme involved in tryptophan catabolism and in quinolinate biosynthesis.";
RL Biochemistry 46:145-155(2007).
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. {ECO:0000255|HAMAP-Rule:MF_01972,
CC ECO:0000269|PubMed:17198384}.
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_01972, ECO:0000269|PubMed:14700627,
CC ECO:0000269|PubMed:17198384};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01972};
CC Note=Binds 1 heme group per subunit. {ECO:0000255|HAMAP-Rule:MF_01972};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=350 uM for tryptophan {ECO:0000269|PubMed:14700627};
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_01972}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01972,
CC ECO:0000269|PubMed:17198384}.
CC -!- SIMILARITY: Belongs to the tryptophan 2,3-dioxygenase family.
CC {ECO:0000255|HAMAP-Rule:MF_01972}.
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DR EMBL; CP000352; ABF09526.1; -; Genomic_DNA.
DR RefSeq; WP_011517225.1; NC_007973.1.
DR PDB; 2NOX; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=19-299.
DR PDBsum; 2NOX; -.
DR AlphaFoldDB; Q1LK00; -.
DR SMR; Q1LK00; -.
DR STRING; 266264.Rmet_2651; -.
DR ChEMBL; CHEMBL1914265; -.
DR PRIDE; Q1LK00; -.
DR EnsemblBacteria; ABF09526; ABF09526; Rmet_2651.
DR KEGG; rme:Rmet_2651; -.
DR eggNOG; COG3483; Bacteria.
DR HOGENOM; CLU_063240_0_0_4; -.
DR OMA; WRWRNDH; -.
DR OrthoDB; 1660023at2; -.
DR SABIO-RK; Q1LK00; -.
DR UniPathway; UPA00333; UER00453.
DR EvolutionaryTrace; Q1LK00; -.
DR Proteomes; UP000002429; Chromosome.
DR GO; GO:1902494; C:catalytic complex; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI: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:0009435; P:NAD biosynthetic process; NAS:UniProtKB.
DR GO; GO:0019805; P:quinolinate biosynthetic process; NAS:UniProtKB.
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; IPR017485; Trp_2-3-dOase_bac.
DR InterPro; IPR004981; Trp_2_3_dOase.
DR PANTHER; PTHR10138; PTHR10138; 2.
DR Pfam; PF03301; Trp_dioxygenase; 1.
DR SUPFAM; SSF140959; SSF140959; 1.
DR TIGRFAMs; TIGR03036; trp_2_3_diox; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Heme; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome; Tryptophan catabolism.
FT CHAIN 1..299
FT /note="Tryptophan 2,3-dioxygenase"
FT /id="PRO_0000360128"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 68..72
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01972"
FT BINDING 130
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01972"
FT BINDING 134
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01972"
FT BINDING 257
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_01972"
FT BINDING 271
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01972"
FT MUTAGEN 68
FT /note="F->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:17198384"
FT MUTAGEN 130
FT /note="Y->F: 15-fold increase in catalytic activity."
FT /evidence="ECO:0000269|PubMed:17198384"
FT MUTAGEN 134
FT /note="R->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:17198384"
FT MUTAGEN 271
FT /note="T->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:17198384"
FT HELIX 43..47
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 65..94
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 98..117
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 127..133
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:2NOX"
FT TURN 137..139
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 146..154
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 160..166
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 170..181
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 234..265
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:2NOX"
FT HELIX 290..298
FT /evidence="ECO:0007829|PDB:2NOX"
SQ SEQUENCE 299 AA; 34304 MW; 735273ABF87FA296 CRC64;
MSEFKGCPMG HGAAPQNGDG GDSGDTGNGW HGAQMDFARD MSYGDYLGLD QILSAQHPLS
PDHNEMLFIV QHQTTELWMK LMLHELRAAR DGVKSDQLQP AFKMLARVSR IMDQLVQAWN
VLATMTPPEY SAMRPYLGAS SGFQSYQYRE IEFILGNKNA AMLRPHAHRP EHLELVETAL
HTPSMYDEAI RLMARRGFQI DPEVVERDWT QPTQYNASVE AAWLEVYRNP SAHWELYELG
EKFVDLEDAF RQWRFRHVTT VERVIGFKRG TGGTEGVSYL RRMLDVVLFP ELWKLRTDL
