TYRDC_ENTFA
ID TYRDC_ENTFA Reviewed; 620 AA.
AC Q838D6;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=L-tyrosine decarboxylase {ECO:0000303|PubMed:30659181};
DE Short=TDC {ECO:0000303|PubMed:30659181};
DE EC=4.1.1.25 {ECO:0000269|PubMed:30659181};
DE AltName: Full=Levodopa decarboxylase {ECO:0000305|PubMed:30659181};
DE Short=L-dopa decarboxylase {ECO:0000305|PubMed:30659181};
DE EC=4.1.1.- {ECO:0000269|PubMed:30659181};
GN Name=tdc {ECO:0000303|PubMed:30659181};
GN Synonyms=tdcA {ECO:0000303|PubMed:25529314};
GN OrderedLocusNames=EF_0634 {ECO:0000312|EMBL:AAO80459.1};
OS Enterococcus faecalis (strain ATCC 700802 / V583).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=226185;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700802 / V583;
RX PubMed=12663927; DOI=10.1126/science.1080613;
RA Paulsen I.T., Banerjei L., Myers G.S.A., Nelson K.E., Seshadri R.,
RA Read T.D., Fouts D.E., Eisen J.A., Gill S.R., Heidelberg J.F., Tettelin H.,
RA Dodson R.J., Umayam L.A., Brinkac L.M., Beanan M.J., Daugherty S.C.,
RA DeBoy R.T., Durkin S.A., Kolonay J.F., Madupu R., Nelson W.C.,
RA Vamathevan J.J., Tran B., Upton J., Hansen T., Shetty J., Khouri H.M.,
RA Utterback T.R., Radune D., Ketchum K.A., Dougherty B.A., Fraser C.M.;
RT "Role of mobile DNA in the evolution of vancomycin-resistant Enterococcus
RT faecalis.";
RL Science 299:2071-2074(2003).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, INDUCTION, AND PATHWAY.
RC STRAIN=ATCC 700802 / V583;
RX PubMed=25529314; DOI=10.1007/s00253-014-6301-7;
RA Perez M., Calles-Enriquez M., Nes I., Martin M.C., Fernandez M., Ladero V.,
RA Alvarez M.A.;
RT "Tyramine biosynthesis is transcriptionally induced at low pH and improves
RT the fitness of Enterococcus faecalis in acidic environments.";
RL Appl. Microbiol. Biotechnol. 99:3547-3558(2015).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP REGULATION.
RC STRAIN=ATCC 700802 / V583;
RX PubMed=30659181; DOI=10.1038/s41467-019-08294-y;
RA van Kessel S.P., Frye A.K., El-Gendy A.O., Castejon M., Keshavarzian A.,
RA van Dijk G., El Aidy S.;
RT "Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the
RT treatment of Parkinson's disease.";
RL Nat. Commun. 10:310-310(2019).
CC -!- FUNCTION: Catalyzes the decarboxylation of L-tyrosine to produce
CC tyramine (PubMed:30659181). Plays a role in acid resistance since
CC tyramine production via tyrosine decarboxylation appears to provide a
CC cytosolic pH maintenance mechanism that helps the bacterium cope with
CC acid stress such as that encountered in gastrointestinal tract (GIT)
CC environments. Therefore, may contribute to the colonization of the
CC human GIT by E.faecalis (PubMed:25529314).
CC {ECO:0000269|PubMed:25529314, ECO:0000269|PubMed:30659181}.
CC -!- FUNCTION: Also involved in drug metabolism, being able to catalyze
CC decarboxylation of levodopa (L-dopa) to dopamine. In gut microbiota
CC this enzyme is in fact exclusively responsible for the decarboxylation
CC of levodopa, and thus reduces in situ levels of levodopa in the
CC treatment of Parkinson's disease. It was shown that abundance of
CC bacterial tyrosine decarboxylase in the proximal small intestine - the
CC primary site of levodopa absorption - contributes to interindividual
CC variation in drug efficacy and can explain the requirement for an
CC increased dosage regimen of levodopa treatment in Parkinson's disease
CC patients. {ECO:0000269|PubMed:30659181}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-tyrosine = CO2 + tyramine; Xref=Rhea:RHEA:14345,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:58315,
CC ChEBI:CHEBI:327995; EC=4.1.1.25;
CC Evidence={ECO:0000269|PubMed:30659181, ECO:0000305|PubMed:25529314};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14346;
CC Evidence={ECO:0000269|PubMed:25529314};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + L-dopa = CO2 + dopamine; Xref=Rhea:RHEA:12272,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57504,
CC ChEBI:CHEBI:59905; Evidence={ECO:0000269|PubMed:30659181};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12273;
CC Evidence={ECO:0000305|PubMed:30659181};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000305|PubMed:30659181};
CC -!- ACTIVITY REGULATION: Levodopa decarboxylation is not inhibited by
CC carbidopa, benserazide, and methyldopa, that are three human L-dopa
CC decarboxylase inhibitors. {ECO:0000269|PubMed:30659181}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.6 mM for L-tyrosine (at pH 5.0) {ECO:0000269|PubMed:30659181};
CC KM=3 mM for L-dopa (at pH 5.0) {ECO:0000269|PubMed:30659181};
CC Vmax=69.6 umol/min/mg enzyme for the decarboxylation of L-tyrosine
CC (at pH 5.0) {ECO:0000269|PubMed:30659181};
CC Vmax=35.3 umol/min/mg enzyme for the decarboxylation of L-dopa (at pH
CC 5.0) {ECO:0000269|PubMed:30659181};
CC Note=kcat is 6963 min(-1) for the decarboxylation of L-tyrosine. kcat
CC is 3531 min(-1) for the decarboxylation of L-dopa (at pH 5.0).
CC {ECO:0000269|PubMed:30659181};
CC -!- PATHWAY: Amino-acid metabolism. {ECO:0000269|PubMed:25529314}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:J7GQ11}.
CC -!- INDUCTION: Up-regulated by tyrosine and acidic pH. Makes part of an
CC operon together with tyrP and nhaC-2. {ECO:0000269|PubMed:25529314}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking the tdc cluster (tyrS, tdc/tdcA,
CC tyrP and nhaC-2) lose the ability to produce tyramine, and show reduced
CC viability under acidic pHs in the presence of tyrosine.
CC {ECO:0000269|PubMed:25529314}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family. Tyrosine
CC decarboxylase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAO80459.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AE016830; AAO80459.1; ALT_INIT; Genomic_DNA.
DR RefSeq; NP_814388.1; NC_004668.1.
DR RefSeq; WP_002355450.1; NC_004668.1.
DR AlphaFoldDB; Q838D6; -.
DR SMR; Q838D6; -.
DR STRING; 226185.EF_0634; -.
DR EnsemblBacteria; AAO80459; AAO80459; EF_0634.
DR GeneID; 60892923; -.
DR KEGG; efa:EF0634; -.
DR PATRIC; fig|226185.9.peg.582; -.
DR eggNOG; COG0076; Bacteria.
DR HOGENOM; CLU_005446_0_1_9; -.
DR BRENDA; 4.1.1.25; 2095.
DR Proteomes; UP000001415; Chromosome.
DR GO; GO:0036468; F:L-dopa decarboxylase activity; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0004837; F:tyrosine decarboxylase activity; IDA:UniProtKB.
DR GO; GO:1903184; P:L-dopa metabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.640.10; -; 1.
DR InterPro; IPR002129; PyrdxlP-dep_de-COase.
DR InterPro; IPR015424; PyrdxlP-dep_Trfase.
DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major.
DR InterPro; IPR022397; Tyrosine_deCO2ase_bac.
DR Pfam; PF00282; Pyridoxal_deC; 2.
DR SUPFAM; SSF53383; SSF53383; 1.
DR TIGRFAMs; TIGR03811; tyr_de_CO2_Ent; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Decarboxylase; Lyase; Pyridoxal phosphate; Reference proteome;
KW Stress response.
FT CHAIN 1..620
FT /note="L-tyrosine decarboxylase"
FT /id="PRO_0000448496"
FT ACT_SITE 420
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT BINDING 158..159
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT BINDING 298
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT BINDING 389..391
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT BINDING 440
FT /ligand="pyridoxal 5'-phosphate"
FT /ligand_id="ChEBI:CHEBI:597326"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT MOD_RES 392
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
SQ SEQUENCE 620 AA; 70053 MW; A83C598048C7D5E1 CRC64;
MKNEKLAKGE MNLNALFIGD KAENGQLYKD LLIDLVDEHL GWRQNYMPQD MPVISSQERT
SESYEKTVNH MKDVLNEISS RMRTHSVPWH TAGRYWGHMN SETLMPSLLA YNFAMLWNGN
NVAYESSPAT SQMEEEVGHE FAHLMSYKNG WGHIVADGSL ANLEGLWYAR NIKSLPFAMK
EVKPELVAGK SDWELLNMPT KEIMDLLESA EDEIDEIKAH SARSGKHLQA IGKWLVPQTK
HYSWLKAADI IGIGLDQVIP VPVDHNYRMD INELEKIVRG LAEEQIPVLG VVGVVGSTEE
GAVDSIDKII ALRDELMKDG IYYYVHVDAA YGGYGRAIFL DEDNNFIPYE DLQDVHEEYG
VFKEKKEHIS REVYDAYKAI ELAESVTIDP HKMGYIPYSA GGIVIQDIRM RDVISYFATY
VFEKGADIPA LLGAYILEGS KAGATAASVW AAHHVLPLNV AGYGKLIGAS IEGSHHFYNF
LNDLTFKVGD KEIEVHTLTH PDFNMVDYVF KEKGNDDLVA MNKLNHDVYD YASYVKGNIY
NNEFITSHTD FAIPDYGNSP LKFVNSLGFS DEEWNRAGKV TVLRAAVMTP YMNDKEEFDV
YAPKIQAALQ EKLEQIYDVK
