IYD_THENN
ID IYD_THENN Reviewed; 186 AA.
AC B9K712;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Iodotyrosine deiodinase {ECO:0000303|PubMed:34748729};
DE EC=1.21.1.1 {ECO:0000269|PubMed:34748729};
DE AltName: Full=Halotyrosine dehalogenase {ECO:0000305|PubMed:34748729};
GN Name=IYD {ECO:0000303|PubMed:34748729};
GN OrderedLocusNames=CTN_0569 {ECO:0000312|EMBL:ACM22745.1};
OS Thermotoga neapolitana (strain ATCC 49049 / DSM 4359 / NBRC 107923 / NS-E).
OC Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX NCBI_TaxID=309803 {ECO:0000312|Proteomes:UP000000445};
RN [1] {ECO:0000312|Proteomes:UP000000445}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 49049 / DSM 4359 / NBRC 107923 / NS-E
RC {ECO:0000312|Proteomes:UP000000445};
RA Lim S.K., Kim J.S., Cha S.H., Park B.C., Lee D.S., Tae H.S., Kim S.-J.,
RA Kim J.J., Park K.J., Lee S.Y.;
RT "The genome sequence of the hyperthermophilic bacterium Thermotoga
RT neapolitana.";
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:6Q1B, ECO:0007744|PDB:6TYK}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH FMN;
RP 3-IODO-L-TYROSINE AND 3-FLUORO-L-TYROSINE.
RA Sun Z., Kavran J.M., Rokita S.E.;
RL Submitted (AUG-2019) to the PDB data bank.
RN [3] {ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6Q1L}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) IN COMPLEX WITH FMN;
RP 3-IODO-L-TYROSINE AND L-TYROSINE, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, SUBUNIT, AND MUTAGENESIS OF
RP MET-41; TRP-82; PHE-88 AND TYR-112.
RC STRAIN=ATCC 49049 / DSM 4359 / NBRC 107923 / NS-E
RC {ECO:0000303|PubMed:34748729};
RX PubMed=34748729; DOI=10.1016/j.jbc.2021.101385;
RA Sun Z., Xu B., Spisak S., Kavran J.M., Rokita S.E.;
RT "The minimal structure for iodotyrosine deiodinase function is defined by
RT an outlier protein from the thermophilic bacterium Thermotoga
RT neapolitana.";
RL J. Biol. Chem. 297:101385-101385(2021).
CC -!- FUNCTION: Catalyzes the dehalogenation of halotyrosines such as 3-
CC bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-
CC diiodo-L-tyrosine (PubMed:34748729). Activity towards 2-iodophenol is
CC weak (PubMed:34748729). {ECO:0000269|PubMed:34748729}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 iodide + L-tyrosine + 2 NADP(+) = 3,5-diiodo-L-tyrosine +
CC H(+) + 2 NADPH; Xref=Rhea:RHEA:32479, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349; EC=1.21.1.1;
CC Evidence={ECO:0000269|PubMed:34748729};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32481;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide + L-tyrosine + NADP(+) = 3-iodo-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:27453, ChEBI:CHEBI:16382, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC Evidence={ECO:0000269|PubMed:34748729};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27455;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-iodo-L-tyrosine + iodide + NADP(+) = 3,5-diiodo-L-tyrosine +
CC H(+) + NADPH; Xref=Rhea:RHEA:27457, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC Evidence={ECO:0000269|PubMed:34748729};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27459;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride + L-tyrosine + NADP(+) = 3-chloro-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:70343, ChEBI:CHEBI:17996, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189422;
CC Evidence={ECO:0000269|PubMed:34748729};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70345;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bromide + L-tyrosine + NADP(+) = 3-bromo-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:70347, ChEBI:CHEBI:15858, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189423;
CC Evidence={ECO:0000269|PubMed:34748729};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70349;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:34748729};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.22 uM for 3-iodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC KM=3.5 uM for 3-iodo-L-tyrosine (at pH 7.4 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC KM=4200 uM for 2-iodophenol (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC KM=0.14 uM for 3-bromo-L-tyrosine (at pH 7.4 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC KM=5 uM for 3-chloro-L-tyrosine (at pH 7.4 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC KM=6600 uM for 2-iodophenol (at pH 7.4 and 60 degrees Celsius)
CC {ECO:0000269|PubMed:34748729};
CC Note=kcat is 1.6 min(-1) for the dehalogenation of 3-iodo-L-tyrosine
CC (at pH 7.4 and 25 degrees Celsius) (PubMed:34748729). kcat is 27
CC min(-1) for the dehalogenation of 3-iodo-L-tyrosine (at pH 7.4 and 60
CC degrees Celsius) (PubMed:34748729). kcat is 0.84 min(-1) for the
CC dehalogenation of 2-iodophenol (at pH 7.4 and 25 degrees Celsius)
CC (PubMed:34748729). kcat is 6.5 min(-1) for the dehalogenation of 2-
CC iodophenol (at pH 7.4 and 60 degrees Celsius) (PubMed:34748729). kcat
CC is 27 min(-1) for the dehalogenation of 3-iodo-L-tyrosine (at pH 7.4
CC and 60 degrees Celsius) (PubMed:34748729). kcat is 5.1 min(-1) for
CC the dehalogenation of 3-bromo-L-tyrosine (at pH 7.4 and 60 degrees
CC Celsius) (PubMed:34748729). kcat is 2.9 min(-1) for the
CC dehalogenation of 3-chloro-L-tyrosine (at pH 7.4 and 60 degrees
CC Celsius) (PubMed:34748729). {ECO:0000269|PubMed:34748729};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:34748729}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
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DR EMBL; CP000916; ACM22745.1; -; Genomic_DNA.
DR PDB; 6PZ0; X-ray; 1.80 A; A/B=1-186.
DR PDB; 6Q1B; X-ray; 1.60 A; A/B=1-186.
DR PDB; 6Q1L; X-ray; 1.60 A; A/B=1-186.
DR PDB; 6TYK; X-ray; 1.35 A; A/B=1-186.
DR PDBsum; 6PZ0; -.
DR PDBsum; 6Q1B; -.
DR PDBsum; 6Q1L; -.
DR PDBsum; 6TYK; -.
DR SMR; B9K712; -.
DR STRING; 309803.CTN_0569; -.
DR EnsemblBacteria; ACM22745; ACM22745; CTN_0569.
DR KEGG; tna:CTN_0569; -.
DR eggNOG; COG0778; Bacteria.
DR HOGENOM; CLU_070764_7_2_0; -.
DR OMA; WVDQDLQ; -.
DR Proteomes; UP000000445; Chromosome.
DR GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR GO; GO:0140616; F:iodotyrosine deiodinase activity; IDA:UniProtKB.
DR GO; GO:0072545; F:tyrosine binding; IDA:UniProtKB.
DR GO; GO:0006570; P:tyrosine metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.109.10; -; 1.
DR InterPro; IPR029479; Nitroreductase.
DR InterPro; IPR000415; Nitroreductase-like.
DR Pfam; PF00881; Nitroreductase; 1.
DR SUPFAM; SSF55469; SSF55469; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Flavoprotein; FMN; NADP; Oxidoreductase.
FT CHAIN 1..186
FT /note="Iodotyrosine deiodinase"
FT /id="PRO_0000455637"
FT BINDING 11..15
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6Q1B,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 38..39
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6Q1B,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 39
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6Q1B,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 41
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 41
FT /ligand="L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:58315"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6TYK"
FT BINDING 68
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 68
FT /ligand="L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:58315"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6TYK"
FT BINDING 72
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 72
FT /ligand="L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:58315"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6TYK"
FT BINDING 92
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT BINDING 92
FT /ligand="L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:58315"
FT /evidence="ECO:0000269|PubMed:34748729,
FT ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6TYK"
FT BINDING 176
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0007744|PDB:6PZ0, ECO:0007744|PDB:6Q1B,
FT ECO:0007744|PDB:6Q1L, ECO:0007744|PDB:6TYK"
FT MUTAGEN 41
FT /note="M->A: Decreases affinity to L-Tyrosine (Tyr) and
FT slightly reduces affinity to 3-iodo-L-tyrosine (I-Tyr)."
FT /evidence="ECO:0000269|PubMed:34748729"
FT MUTAGEN 41
FT /note="M->F: Increases affinity to Tyr and decreases
FT affinity to I-Tyr."
FT /evidence="ECO:0000269|PubMed:34748729"
FT MUTAGEN 41
FT /note="M->K: Decreases affinity for I-Tyr and Tyr."
FT /evidence="ECO:0000269|PubMed:34748729"
FT MUTAGEN 82
FT /note="W->A: Strongly reduces affinity for Tyr by more than
FT more than 2600-fold and reduces affinity for I-Tyr by 18-
FT fold; when associated with A-88 and A-112."
FT /evidence="ECO:0000269|PubMed:34748729"
FT MUTAGEN 88
FT /note="F->A: Strongly reduces affinity for Tyr by more than
FT more than 2600-fold and reduces affinity for I-Tyr by 18-
FT fold; when associated with A-82 and A-112."
FT /evidence="ECO:0000269|PubMed:34748729"
FT MUTAGEN 112
FT /note="Y->A: No effect on binding to I-Tyr and Tyr.
FT Strongly reduces affinity for Tyr by more than more than
FT 2600-fold and reduces affinity for I-Tyr by 18-fold; when
FT associated with A-82 and A-88."
FT /evidence="ECO:0000269|PubMed:34748729"
SQ SEQUENCE 186 AA; 22028 MW; B229B9C45B6BFFF2 CRC64;
MKMLYDLAKK RKTVRRFKKE KPPLEDLIYS LKVANEAPSG MNAQPWRFLI VEDEKLKGQI
RRVCERSEKT FYENVRGRLK EWLDEKRFTW RKPFLKEAPY LLLVFSEKSA PYSRESVWLA
VGYLLLALEE KGLGSVPYTP PDFREVEKLV NTPSELRLEV ILPVGYPDDP KPKYPRNEVI
VRYNTF
