FLDH_CLOS1
ID FLDH_CLOS1 Reviewed; 331 AA.
AC J7SHB8;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Aromatic 2-oxoacid reductase {ECO:0000305};
DE EC=1.1.1.110 {ECO:0000269|PubMed:29168502, ECO:0000269|PubMed:4384683};
DE AltName: Full=Indolelactate dehydrogenase {ECO:0000303|PubMed:4384683};
GN Name=fldH {ECO:0000303|PubMed:29168502};
GN ORFNames=CLOSPO_00316 {ECO:0000312|EMBL:EDU39261.1};
OS Clostridium sporogenes (strain ATCC 15579).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=471871;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15579;
RA Sudarsanam P., Ley R., Guruge J., Turnbaugh P.J., Mahowald M., Liep D.,
RA Gordon J., Fulton L., Clifton S., Fulton B., Xu J., Minx P., Pepin K.H.,
RA Johnson M., Thiruvilangam P., Bhonagiri V., Nash W.E., Mardis E.R.,
RA Wilson R.K.;
RT "Draft genome sequence of Clostridium sporogenes ATCC 15579.";
RL Submitted (MAY-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=175;
RX PubMed=4384683; DOI=10.1139/m68-068;
RA Jean M., DeMoss R.D.;
RT "Indolelactate dehydrogenase from Clostridium sporogenes.";
RL Can. J. Microbiol. 14:429-435(1968).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND PATHWAY.
RC STRAIN=ATCC 15579;
RX PubMed=29168502; DOI=10.1038/nature24661;
RA Dodd D., Spitzer M.H., Van Treuren W., Merrill B.D., Hryckowian A.J.,
RA Higginbottom S.K., Le A., Cowan T.M., Nolan G.P., Fischbach M.A.,
RA Sonnenburg J.L.;
RT "A gut bacterial pathway metabolizes aromatic amino acids into nine
RT circulating metabolites.";
RL Nature 551:648-652(2017).
CC -!- FUNCTION: Essential for the reductive metabolism of L-phenylalanine, L-
CC tyrosine and L-tryptophan (PubMed:29168502). Catalyzes the conversion
CC of phenylpyruvic acid to phenyllactic acid, 4-hydroxy-phenylpyruvic
CC acid to 4-hydroxy-phenyllactic acid, and indolepyruvic acid to
CC indolelactic acid (PubMed:29168502, PubMed:4384683).
CC {ECO:0000269|PubMed:29168502, ECO:0000269|PubMed:4384683}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-3-phenyllactate + NAD(+) = 3-phenylpyruvate + H(+) + NADH;
CC Xref=Rhea:RHEA:38351, ChEBI:CHEBI:11009, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:18005, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.110; Evidence={ECO:0000269|PubMed:29168502,
CC ECO:0000269|PubMed:4384683};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38353;
CC Evidence={ECO:0000269|PubMed:29168502};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R)-2-hydroxy-3-(4-hydroxyphenyl)propanoate + NAD(+) = 3-(4-
CC hydroxyphenyl)pyruvate + H(+) + NADH; Xref=Rhea:RHEA:10780,
CC ChEBI:CHEBI:10980, ChEBI:CHEBI:15378, ChEBI:CHEBI:36242,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.110;
CC Evidence={ECO:0000269|PubMed:29168502, ECO:0000269|PubMed:4384683};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10782;
CC Evidence={ECO:0000269|PubMed:29168502};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(indol-3-yl)lactate + NAD(+) = H(+) + indole-3-pyruvate +
CC NADH; Xref=Rhea:RHEA:20133, ChEBI:CHEBI:15378, ChEBI:CHEBI:17282,
CC ChEBI:CHEBI:17640, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945;
CC EC=1.1.1.110; Evidence={ECO:0000269|PubMed:29168502,
CC ECO:0000269|PubMed:4384683};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:20135;
CC Evidence={ECO:0000269|PubMed:29168502};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.075 mM for p-hydroxyphenylpyruvate {ECO:0000269|PubMed:4384683};
CC KM=0.106 mM for phenylpyruvate {ECO:0000269|PubMed:4384683};
CC KM=0.0142 mM for NADH (in the presence of indolepyruvate)
CC {ECO:0000269|PubMed:4384683};
CC KM=1.03 mM for indolelactate {ECO:0000269|PubMed:4384683};
CC KM=1.77 mM for p-hydroxyphenyllactate {ECO:0000269|PubMed:4384683};
CC KM=2.21 mM for phenyllactate {ECO:0000269|PubMed:4384683};
CC KM=0.691 mM for indoleglycollate {ECO:0000269|PubMed:4384683};
CC KM=0.195 mM for NAD(+) (in the presence of indolelactate)
CC {ECO:0000269|PubMed:4384683};
CC pH dependence:
CC Optimum pH is 7.0 for indolepyruvate reduction. Optimum pH is 8.5 for
CC indolelactate oxidation. {ECO:0000269|PubMed:4384683};
CC -!- PATHWAY: Amino-acid degradation. {ECO:0000269|PubMed:29168502}.
CC -!- DISRUPTION PHENOTYPE: Mutants are deficient in reductive metabolism of
CC phenylalanine, tyrosine and tryptophan, and exhibit growth defects when
CC cultured with amino acids as the sole carbon source.
CC {ECO:0000269|PubMed:29168502}.
CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; ABKW02000002; EDU39261.1; -; Genomic_DNA.
DR RefSeq; WP_003483291.1; NZ_DS981517.1.
DR EnsemblBacteria; EDU39261; EDU39261; CLOSPO_00316.
DR HOGENOM; CLU_019796_1_1_9; -.
DR Proteomes; UP000006610; Unassembled WGS sequence.
DR GO; GO:0033711; F:4-phosphoerythronate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0047995; F:hydroxyphenylpyruvate reductase activity; IEA:RHEA.
DR GO; GO:0047722; F:indolelactate dehydrogenase (NADH) activity; IEA:RHEA.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0097256; F:phenyllactate dehydrogenase activity; IEA:RHEA.
DR GO; GO:0006559; P:L-phenylalanine catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006569; P:tryptophan catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006572; P:tyrosine catabolic process; IEA:UniProtKB-KW.
DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom.
DR InterPro; IPR029753; D-isomer_DH_CS.
DR InterPro; IPR029752; D-isomer_DH_CS1.
DR InterPro; IPR006140; D-isomer_DH_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00389; 2-Hacid_dh; 1.
DR Pfam; PF02826; 2-Hacid_dh_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1.
DR PROSITE; PS00670; D_2_HYDROXYACID_DH_2; 1.
DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Phenylalanine catabolism; Tryptophan catabolism;
KW Tyrosine catabolism.
FT CHAIN 1..331
FT /note="Aromatic 2-oxoacid reductase"
FT /id="PRO_0000454347"
FT ACT_SITE 234
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT ACT_SITE 263
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT ACT_SITE 295
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 154..155
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 175
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 205..206
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 211
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 232..234
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
FT BINDING 258
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P26297"
SQ SEQUENCE 331 AA; 36592 MW; 5928377166455693 CRC64;
MKILAYCVRP DEIDSFKNFS EKYGHTVDLI PDSFGPNVAH LAKGYDGISI LGNDTCNREA
LEKIKDCGIK YLATRTAGVN NIDFDAAKEF GINVANVPAY SPNSVSEFTV GLALSLTRKI
PFALKRVELN NFALGGLIGV ELRNLTLGVI GTGRIGLKVI EGFSGFGMKK MIGYDIFENE
KAKEYIEYKS LDEVYKEADI ITLHAPLTDD NYHMIGKESI AKMKDGVFII NAARGALIDS
EALIEGLKSG KIAGAALDSY EYEQGVFHNN KMNEIMKDDT LERLKSFPNV VITPHLGFYT
DEAVSNMVEI TLMNLQEFEL KGTCKNQRVC K
