TAM_STRGL
ID TAM_STRGL Reviewed; 539 AA.
AC Q8GMG0;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=MIO-dependent tyrosine 2,3-aminomutase;
DE EC=5.4.3.6;
DE AltName: Full=Tyrosine ammonia-lyase;
DE EC=4.3.1.23;
OS Streptomyces globisporus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1908;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN THE BIOSYNTHESIS OF
RP ENEDIYNE ANTITUMOR ANTIBIOTIC.
RC STRAIN=C-1027;
RX PubMed=12183628; DOI=10.1126/science.1072110;
RA Liu W., Christenson S.D., Standage S., Shen B.;
RT "Biosynthesis of the enediyne antitumor antibiotic C-1027.";
RL Science 297:1170-1173(2002).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS), FUNCTION, DEHYDRATION AT SER-153,
RP CYCLIZATION AT ALA-152 AND GLY-154, AND SUBUNIT.
RX PubMed=17516659; DOI=10.1021/bi7003685;
RA Christianson C.V., Montavon T.J., Van Lanen S.G., Shen B., Bruner S.D.;
RT "The structure of L-tyrosine 2,3-aminomutase from the C-1027 enediyne
RT antitumor antibiotic biosynthetic pathway.";
RL Biochemistry 46:7205-7214(2007).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 12-539, ACTIVE SITE, AND SUBUNIT.
RX PubMed=18078753; DOI=10.1016/j.bmcl.2007.11.046;
RA Montavon T.J., Christianson C.V., Festin G.M., Shen B., Bruner S.D.;
RT "Design and characterization of mechanism-based inhibitors for the tyrosine
RT aminomutase SgTAM.";
RL Bioorg. Med. Chem. Lett. 18:3099-3102(2008).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF MUTANT PHE-63 IN COMPLEX WITH
RP SUBSTRATE, FUNCTION, CATALYTIC ACTIVITY, PTM, MUTAGENESIS OF TYR-63;
RP GLU-71; HIS-93; TYR-303 AND TYR-415, SUBSTRATE SPECIFICITY, AND SUBUNIT.
RX PubMed=20577998; DOI=10.1002/bip.21500;
RA Cooke H.A., Bruner S.D.;
RT "Probing the active site of MIO-dependent aminomutases, key catalysts in
RT the biosynthesis of beta-amino acids incorporated in secondary
RT metabolites.";
RL Biopolymers 93:802-810(2010).
CC -!- FUNCTION: Involved in the biosynthesis of the enediyne antitumor
CC antibiotic C-1027. Catalyzes the MIO-dependent deamination of L-
CC tyrosine generating the corresponding alpha,beta-unsaturated acid, (S)-
CC beta-tyrosine. {ECO:0000269|PubMed:12183628,
CC ECO:0000269|PubMed:17516659, ECO:0000269|PubMed:20577998}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosine = 3-amino-3-(4-hydroxyphenyl)propanoate;
CC Xref=Rhea:RHEA:15781, ChEBI:CHEBI:57956, ChEBI:CHEBI:58315;
CC EC=5.4.3.6; Evidence={ECO:0000269|PubMed:20577998};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosine = (E)-4-coumarate + NH4(+); Xref=Rhea:RHEA:24906,
CC ChEBI:CHEBI:12876, ChEBI:CHEBI:28938, ChEBI:CHEBI:58315; EC=4.3.1.23;
CC Evidence={ECO:0000269|PubMed:20577998};
CC -!- SUBUNIT: Homotetramer; dimer of dimers. {ECO:0000269|PubMed:17516659,
CC ECO:0000269|PubMed:18078753, ECO:0000269|PubMed:20577998}.
CC -!- PTM: Contains an active site 4-methylidene-imidazol-5-one (MIO), which
CC is formed autocatalytically by cyclization and dehydration of residues
CC Ala-Ser-Gly. {ECO:0000269|PubMed:17516659, ECO:0000305}.
CC -!- SIMILARITY: Belongs to the TAL/TAM family. {ECO:0000305}.
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DR EMBL; AY048670; AAL06680.1; -; Genomic_DNA.
DR PDB; 2OHY; X-ray; 2.50 A; A/B=1-539.
DR PDB; 2QVE; X-ray; 2.00 A; A/B=12-539.
DR PDB; 2RJR; X-ray; 2.10 A; A/B=1-539.
DR PDB; 2RJS; X-ray; 2.40 A; A/B=1-539.
DR PDB; 3KDY; X-ray; 2.20 A; A/B=1-539.
DR PDB; 3KDZ; X-ray; 2.20 A; A/B=1-539.
DR PDBsum; 2OHY; -.
DR PDBsum; 2QVE; -.
DR PDBsum; 2RJR; -.
DR PDBsum; 2RJS; -.
DR PDBsum; 3KDY; -.
DR PDBsum; 3KDZ; -.
DR AlphaFoldDB; Q8GMG0; -.
DR SMR; Q8GMG0; -.
DR DrugBank; DB06946; (2S,3S)-3-(4-fluorophenyl)-2,3-dihydroxypropanoic acid.
DR EvolutionaryTrace; Q8GMG0; -.
DR GO; GO:0050368; F:tyrosine 2,3-aminomutase activity; IDA:UniProtKB.
DR GO; GO:0052883; F:tyrosine ammonia-lyase activity; IDA:UniProtKB.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009403; P:toxin biosynthetic process; IDA:UniProtKB.
DR CDD; cd00332; PAL-HAL; 1.
DR Gene3D; 1.10.275.10; -; 1.
DR InterPro; IPR001106; Aromatic_Lyase.
DR InterPro; IPR024083; Fumarase/histidase_N.
DR InterPro; IPR008948; L-Aspartase-like.
DR InterPro; IPR022313; Phe/His_NH3-lyase_AS.
DR InterPro; IPR022314; Tyr_aminomutase.
DR PANTHER; PTHR10362; PTHR10362; 1.
DR Pfam; PF00221; Lyase_aromatic; 1.
DR SUPFAM; SSF48557; SSF48557; 1.
DR TIGRFAMs; TIGR03832; Tyr_2_3_mutase; 1.
DR PROSITE; PS00488; PAL_HISTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Isomerase; Lyase.
FT CHAIN 1..539
FT /note="MIO-dependent tyrosine 2,3-aminomutase"
FT /id="PRO_0000424197"
FT ACT_SITE 63
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:18078753"
FT BINDING 93
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20577998"
FT BINDING 205
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20577998"
FT BINDING 311
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:20577998"
FT MOD_RES 153
FT /note="2,3-didehydroalanine (Ser)"
FT /evidence="ECO:0000269|PubMed:17516659"
FT CROSSLNK 152..154
FT /note="5-imidazolinone (Ala-Gly)"
FT /evidence="ECO:0000269|PubMed:17516659"
FT MUTAGEN 63
FT /note="Y->F: Complete loss of activity. It does not affect
FT the over-all structure of the enzyme."
FT /evidence="ECO:0000269|PubMed:20577998"
FT MUTAGEN 71
FT /note="E->A: Despite a decrease in activity, it shows lyase
FT activity over time and still produced some amount of beta-
FT tyrosine."
FT /evidence="ECO:0000269|PubMed:20577998"
FT MUTAGEN 93
FT /note="H->F: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:20577998"
FT MUTAGEN 303
FT /note="Y->A: Despite a decrease in activity, it shows lyase
FT activity over time and still produced some amount of beta-
FT tyrosine."
FT /evidence="ECO:0000269|PubMed:20577998"
FT MUTAGEN 415
FT /note="Y->V: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:20577998"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 22..30
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 39..56
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 57..59
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 70..74
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 82..92
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 103..117
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 126..137
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 156..166
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 170..174
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 181..186
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 187..189
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 199..204
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 208..238
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 248..250
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 251..254
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 258..271
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 280..290
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 313..335
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 359..387
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 389..391
FT /evidence="ECO:0007829|PDB:2QVE"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 397..399
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 411..424
FT /evidence="ECO:0007829|PDB:2QVE"
FT TURN 438..441
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 448..480
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 483..485
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 488..500
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 511..522
FT /evidence="ECO:0007829|PDB:2QVE"
FT HELIX 525..533
FT /evidence="ECO:0007829|PDB:2QVE"
SQ SEQUENCE 539 AA; 58139 MW; E0CE3B75B579B1D9 CRC64;
MALTQVETEI VPVSVDGETL TVEAVRRVAE ERATVDVPAE SIAKAQKSRE IFEGIAEQNI
PIYGVTTGYG EMIYMQVDKS KEVELQTNLV RSHSAGVGPL FAEDEARAIV AARLNTLAKG
HSAVRPIILE RLAQYLNEGI TPAIPEIGSL GASGDLAPLS HVASTLIGEG YVLRDGRPVE
TAQVLAERGI EPLELRFKEG LALINGTSGM TGLGSLVVGR ALEQAQQAEI VTALLIEAVR
GSTSPFLAEG HDIARPHEGQ IDTAANMRAL MRGSGLTVEH ADLRRELQKD KEAGKDVQRS
EIYLQKAYSL RAIPQVVGAV RDTLYHARHK LRIELNSAND NPLFFEGKEI FHGANFHGQP
IAFAMDFVTI ALTQLGVLAE RQINRVLNRH LSYGLPEFLV SGDPGLHSGF AGAQYPATAL
VAENRTIGPA STQSVPSNGD NQDVVSMGLI SARNARRVLS NNNKILAVEY LAAAQAVDIS
GRFDGLSPAA KATYEAVRRL VPTLGVDRYM ADDIELVADA LSRGEFLRAI ARETDIQLR
