TYRDC_ENTFC
ID TYRDC_ENTFC Reviewed; 611 AA.
AC A0A481NV25;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
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=mfnA_1 {ECO:0000312|EMBL:QAV53955.1};
OS Enterococcus faecium (Streptococcus faecium).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=1352;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC STRAIN=W54;
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.faecium (By similarity). {ECO:0000250|UniProtKB:Q838D6,
CC 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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14346;
CC Evidence={ECO:0000305|PubMed:30659181};
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=0.2 mM for L-tyrosine (at pH 5.0) {ECO:0000269|PubMed:30659181};
CC KM=0.4 mM for L-dopa (at pH 5.0) {ECO:0000269|PubMed:30659181};
CC Vmax=4.4 umol/min/mg enzyme for the decarboxylation of L-tyrosine (at
CC pH 5.0) {ECO:0000269|PubMed:30659181};
CC Vmax=3.4 umol/min/mg enzyme for the decarboxylation of L-dopa (at pH
CC 5.0) {ECO:0000269|PubMed:30659181};
CC Note=kcat is 435.6 min(-1) for the decarboxylation of L-tyrosine.
CC kcat is 342.4 min(-1) for the decarboxylation of L-dopa (at pH 5.0).
CC {ECO:0000269|PubMed:30659181};
CC -!- PATHWAY: Amino-acid metabolism. {ECO:0000305|PubMed:30659181}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:J7GQ11}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family. Tyrosine
CC decarboxylase subfamily. {ECO:0000305}.
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DR EMBL; MH358384; QAV53955.1; -; Genomic_DNA.
DR RefSeq; WP_002342784.1; NZ_PUBI01000015.1.
DR AlphaFoldDB; A0A481NV25; -.
DR SMR; A0A481NV25; -.
DR STRING; 1352.AL014_10560; -.
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; IPR021115; Pyridoxal-P_BS.
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.
DR PROSITE; PS00392; DDC_GAD_HDC_YDC; 1.
PE 1: Evidence at protein level;
KW Coiled coil; Decarboxylase; Lyase; Pyridoxal phosphate.
FT CHAIN 1..611
FT /note="L-tyrosine decarboxylase"
FT /id="PRO_0000448495"
FT ACT_SITE 413
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
FT BINDING 151..152
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 292
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 382..384
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 433
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 385
FT /note="N6-(pyridoxal phosphate)lysine"
FT /evidence="ECO:0000250|UniProtKB:J7GQ11"
SQ SEQUENCE 611 AA; 69341 MW; 8947487FAF220102 CRC64;
MKDMDIKAVF IGDKAENGPV YKMLLNKMVD EHLGWRENYI PSDMPAISEG DKLTPDYLAT
RDHMIEVLDE VSQRLRAGSI PWHSAGRYWG QMNAETLMPA LLAYNYAMLW NPNNVALESS
MATSQMEAEV GQDFASLFNM ADGWGHIAAD GSIANLEGLW YARCIKSIPL AVKEVLPEKV
KNMSEWALLN LSVEEILEMT ESFTDEEMDE VKAASSRSGK NIQKLGKWLV PQTKHYSWMK
ALDICGVGLD QMVAIPVQED YRMDINALEK TIRELADQKI PILGVVAVVG TTEEGQVDSV
DKIIQLREKL KDEGIYFYLH VDAAYGGYAR SLFLNEAGEF VPYASLAEFF EEHHVFHHYV
TIDKEVYEGF RAISEADSVT IDPHKMGYVP YAAGGIVIKH KNMRNIISYF APYVFEKSVK
APDMLGAYIL EGSKAGATAA AVWTAHRVLP LNVTGYGQLI GASIEAAQRF REFLEQLHFT
VKGKTIEVYP LNHPDFNMVN WVFKVQDCTD LNAINELNEK MFDRSSYMDG DVYGERFITS
HTTFTQEDYG DSPIRFIERM GLSKEEWQKE QQITLLRAAI MTPYLNDDRI FNFYTKEIAK
AMEKKLNEII K
