DADH_EGGLN
ID DADH_EGGLN Reviewed; 1017 AA.
AC A0A369NIV7;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Dopamine dehydroxylase {ECO:0000303|PubMed:31196984};
DE EC=1.1.-.- {ECO:0000269|PubMed:31196984};
DE Flags: Precursor;
GN Name=dadH {ECO:0000303|PubMed:31196984};
GN ORFNames=C1859_04790 {ECO:0000312|EMBL:RDC20416.1};
OS Eggerthella lenta (Eubacterium lentum).
OC Bacteria; Actinobacteria; Coriobacteriia; Eggerthellales; Eggerthellaceae;
OC Eggerthella.
OX NCBI_TaxID=84112;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AB12 #2;
RX PubMed=29761785; DOI=10.7554/elife.33953;
RA Koppel N., Bisanz J.E., Pandelia M.E., Turnbaugh P.J., Balskus E.P.;
RT "Discovery and characterization of a prevalent human gut bacterial enzyme
RT sufficient for the inactivation of a family of plant toxins.";
RL Elife 7:E33953-E33953(2018).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND COFACTOR.
RC STRAIN=A2;
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: Involved in drug metabolism, as part of an interspecies gut
CC bacterial pathway for Levodopa (L-dopa) metabolism, acting on dopamine
CC produced by Enterecoccus L-dopa decarboxylase. Removes the para
CC hydroxyl group of dopamine to produce m-tyramine (3-tyramine). It is
CC possible that dopamine dehydroxylation influences the multiple side
CC effects of L-dopa administration linked to dopamine production in the
CC treatment of Parkinson's disease. {ECO:0000269|PubMed:31196984}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + dopamine = 3-tyramine + A + H2O; Xref=Rhea:RHEA:61520,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:59905, ChEBI:CHEBI:144800;
CC Evidence={ECO:0000269|PubMed:31196984};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P07658};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:P07658};
CC -!- COFACTOR:
CC Name=Mo-bis(molybdopterin guanine dinucleotide);
CC Xref=ChEBI:CHEBI:60539; Evidence={ECO:0000269|PubMed:31196984};
CC Note=Binds 1 molybdenum-bis(molybdopterin guanine dinucleotide) (Mo-
CC bis-MGD) cofactor per subunit. {ECO:0000250|UniProtKB:P07658};
CC -!- INDUCTION: Up-regulated in response to dopamine.
CC {ECO:0000269|PubMed:31196984}.
CC -!- PTM: Predicted to be exported by the Tat system. The position of the
CC signal peptide cleavage has not been experimentally proven.
CC {ECO:0000255|PROSITE-ProRule:PRU00648}.
CC -!- MISCELLANEOUS: Although all E.lenta strains examined are dopamine-
CC inducible, less than 50% dehydroxylate dopamine. Intriguingly, this is
CC due to the presence of a single-nucleotide polymorphism (SNP) that
CC results in an Arg-506 to Ser substitution that inactivates the enzyme.
CC {ECO:0000269|PubMed:31196984}.
CC -!- SIMILARITY: Belongs to the prokaryotic molybdopterin-containing
CC oxidoreductase family. {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; PPUK01000004; RDC20416.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A369NIV7; -.
DR SMR; A0A369NIV7; -.
DR BioCyc; MetaCyc:MON-21043; -.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0018818; F:acetylene hydratase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043546; F:molybdopterin cofactor binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:1903184; P:L-dopa metabolic process; IDA:UniProtKB.
DR CDD; cd02781; MopB_CT_Acetylene-hydratase; 1.
DR InterPro; IPR009010; Asp_de-COase-like_dom_sf.
DR InterPro; IPR037949; MopB_CT_Acetylene-hydratase.
DR InterPro; IPR006657; MoPterin_dinucl-bd_dom.
DR InterPro; IPR006656; Mopterin_OxRdtase.
DR InterPro; IPR006963; Mopterin_OxRdtase_4Fe-4S_dom.
DR InterPro; IPR006311; TAT_signal.
DR Pfam; PF00384; Molybdopterin; 1.
DR Pfam; PF01568; Molydop_binding; 1.
DR SMART; SM00926; Molybdop_Fe4S4; 1.
DR SUPFAM; SSF50692; SSF50692; 1.
DR PROSITE; PS51669; 4FE4S_MOW_BIS_MGD; 1.
DR PROSITE; PS51318; TAT; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Iron; Iron-sulfur; Metal-binding; Molybdenum; Oxidoreductase;
KW Signal.
FT SIGNAL 1..34
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 35..1017
FT /note="Dopamine dehydroxylase"
FT /id="PRO_5016629686"
FT DOMAIN 45..103
FT /note="4Fe-4S Mo/W bis-MGD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01004"
FT ACT_SITE 91
FT /note="Electron donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P07658"
FT BINDING 53
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P07658"
FT BINDING 56
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P07658"
FT BINDING 61
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P07658"
FT BINDING 89
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P07658"
FT SITE 506
FT /note="Crucial for dopamine dehydroxylation activity"
FT /evidence="ECO:0000269|PubMed:31196984"
SQ SEQUENCE 1017 AA; 115026 MW; 639E441B1C898ECD CRC64;
MGNLTMSRRT FVKTAAITGA AAAAFGASTH TALAEETYSS VSGNDTVAVK TCCRGCGKME
CGVKVIVQNG RAIRVEGDEG AFQSMGNCCT KSQSSIQAAY HPDRLHYPMK RTNPKGEEPG
WQRISWDEAM QSIVDNFMDI KAKHGGEAIA CQVGTSRIWC MHSESILKNM LETPNNVEAW
QICKGPRHFA TTMVSQFAMS WMETITRPKV YVQWGGASEL SNYDDSCRTT VDVASRADVH
ISVDPRMANM GKEADYWQHL RPGTDGALAL AWTNVIIEKK LYDELYVKKW TNAPFLVCED
MEPSGFPTVR TDGSYWDVKT ALLKESDIKE GGSPYKFLVY DNNWEKLKAE GVEHEYGAFT
WFNADQEGVI DETGGFWEGE NYDSEKARQG REAAQDNLLP GQTQGWLPDP MPFDPAIDPA
LEGEFEITLK DGKTVKVKPV WEHYKARAAE YKPEVAAEIT GIPASEIEAA ATAYGTRIDP
STGYGNGGIQ YMLAVEHFCS AIQNCRAFDN LVGITGNMDT PGGNRGPTIV PIDGDLQGFS
AWAPGATTPP EEVNRKQIGI DKFPLLGWWQ YWCDSHSLWD AVITGDPYPV RALWNESGNF
MSQTNTTRAW EALCSLDFYV DLNLWHTPQN DTADIILPVA HWIELNSPRA SQGSAGAMGA
TVKCVQPPAE AKYDPEIVMD LARRMNWKWT DEPGNEWPDI NWQLDDSIKL LTDDELTYTT
WHVENGKPTF ERHGVPMAEV TPKYKTWDEY VKAFQEHGWW QAKDIEPRNW GTYRRYQTGA
MRARDRVWGR LDYTAGKGIG DWKPGWFTPT MKQEIWSTVM ESHHPDHPEW RLPTYTEPPH
GPKDGDRIKE YPLTATTGRR IPVYFHSEHR QLPWCRELWP VPRVEINPKT AAEYGIEQGD
WVWIETEWGK IREVADLYYG VKEDVINLEH TWWYPEVKDA GHGWQFSQVN QLIDHYAQDP
HSGTSNLRAY QVKIYKATPE NSPFNNPVPC DSTGTPIIHT SDDPRLKEWL PTYEGRE
