TYRDC_ENTF3
ID TYRDC_ENTF3 Reviewed; 620 AA.
AC P0DTQ4;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 1.
DT 03-AUG-2022, entry version 12.
DE RecName: Full=L-tyrosine decarboxylase {ECO:0000303|PubMed:31196984};
DE Short=TDC;
DE Short=TyrDC {ECO:0000303|PubMed:31196984};
DE EC=4.1.1.25 {ECO:0000269|PubMed:31196984};
DE AltName: Full=Levodopa decarboxylase {ECO:0000305|PubMed:31196984};
DE Short=L-dopa decarboxylase {ECO:0000305|PubMed:31196984};
DE EC=4.1.1.- {ECO:0000269|PubMed:31196984};
GN Name=tyrDC {ECO:0000303|PubMed:31196984};
GN ORFNames=EFMMH594_12992 {ECO:0000312|EMBL:KKA47138.1};
OS Enterococcus faecalis (strain EnGen0310 / MMH594).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=1158653;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=EnGen0310 / MMH594;
RA Leanti La Rosa S., Nes I.F., Diep D.B., Brede D.A.;
RT "Genome Sequence of the nosocomial blood isolate Enterococcus faecalis
RT MMH594.";
RL Submitted (JAN-2013) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=EnGen0310 / MMH594;
RX PubMed=31196984; DOI=10.1126/science.aau6323;
RA Maini Rekdal V., Bess E.N., Bisanz J.E., Turnbaugh P.J., Balskus E.P.;
RT "Discovery and inhibition of an interspecies gut bacterial pathway for
RT Levodopa metabolism.";
RL Science 364:0-0(2019).
CC -!- FUNCTION: Catalyzes the decarboxylation of L-tyrosine to produce
CC tyramine (PubMed:31196984). 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 (By similarity). {ECO:0000250|UniProtKB:Q838D6,
CC ECO:0000269|PubMed:31196984}.
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:31196984}.
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:31196984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14346;
CC Evidence={ECO:0000305|PubMed:31196984};
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:31196984};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12273;
CC Evidence={ECO:0000269|PubMed:31196984};
CC -!- COFACTOR:
CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC Evidence={ECO:0000305|PubMed:31196984};
CC -!- ACTIVITY REGULATION: (S)-alpha-fluoromethyltyrosine (AFMT) specifically
CC inhibits microbial L-dopa decarboxylase activity, including in
CC Parkinson's disease patient microbiotas. AFMT shows potential to block
CC degradation of L-dopa by E.faecalis in mice. Blocking bacterial L-dopa
CC decarboxylase activity in patients with Parkinson's disease, with
CC knowledge of the abundance of this enzyme in an individual, could
CC personalize and potentially improve L-dopa therapies. In contrast, L-
CC dopa decarboxylation by E.faecalis is not inhibited by carbidopa, a
CC commonly used human L-dopa decarboxylase inhibitor.
CC {ECO:0000269|PubMed:31196984}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=315 uM for L-tyrosine (at pH 5.5);
CC KM=1475 uM for L-dopa (at pH 5.5);
CC Note=kcat is 63.6 sec(-1) for the decarboxylation of L-tyrosine. kcat
CC is 55.5 sec(-1) for the decarboxylation of L-dopa (at pH 5.5).
CC {ECO:0000269|PubMed:31196984};
CC pH dependence:
CC L-dopa decarboxylation occurs more rapidly at lower pH, suggesting
CC that this metabolism is likely accelerated at the lower pH of the
CC upper small intestine. {ECO:0000269|PubMed:31196984};
CC -!- PATHWAY: Amino-acid metabolism. {ECO:0000305|PubMed:31196984}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:J7GQ11}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene lose the ability to
CC decarboxylate L-dopa, and display no growth defects compared with wild
CC type. {ECO:0000269|PubMed:31196984}.
CC -!- SIMILARITY: Belongs to the group II decarboxylase family. Tyrosine
CC decarboxylase subfamily. {ECO:0000305}.
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DR EMBL; AOPW01000049; KKA47138.1; -; Genomic_DNA.
DR RefSeq; WP_002355450.1; NZ_AOPW01000049.1.
DR AlphaFoldDB; P0DTQ4; -.
DR SMR; P0DTQ4; -.
DR GeneID; 60892923; -.
DR BioCyc; MetaCyc:MON-21044; -.
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 Decarboxylase; Lyase; Pyridoxal phosphate.
FT CHAIN 1..620
FT /note="L-tyrosine decarboxylase"
FT /id="PRO_0000448498"
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
