LARE_LACPL
ID LARE_LACPL Reviewed; 276 AA.
AC F9UST4;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 64.
DE RecName: Full=Pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase {ECO:0000305};
DE EC=4.4.1.37 {ECO:0000269|PubMed:27114550};
DE AltName: Full=Lactate racemase accessory protein LarE {ECO:0000303|PubMed:24710389};
DE AltName: Full=Lactate racemase activation protein LarE {ECO:0000303|PubMed:24710389};
DE AltName: Full=Lactate racemase maturation protein LarE {ECO:0000303|PubMed:24710389};
DE AltName: Full=Lactate racemization operon protein LarE {ECO:0000303|PubMed:16166538, ECO:0000312|EMBL:CCC77665.1};
DE AltName: Full=Nickel-pincer cofactor biosynthesis protein LarE {ECO:0000305|PubMed:27114550};
DE AltName: Full=Pyridinium-3,5-biscarboxylic acid mononucleotide sulfurtransferase {ECO:0000305|PubMed:27114550};
DE Short=P2CMN sulfurtransferase {ECO:0000305|PubMed:27114550};
GN Name=larE {ECO:0000303|PubMed:16166538, ECO:0000312|EMBL:CCC77665.1};
GN OrderedLocusNames=lp_0109 {ECO:0000312|EMBL:CCC77665.1};
OS Lactiplantibacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1)
OS (Lactobacillus plantarum).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lactiplantibacillus.
OX NCBI_TaxID=220668;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=12566566; DOI=10.1073/pnas.0337704100;
RA Kleerebezem M., Boekhorst J., van Kranenburg R., Molenaar D., Kuipers O.P.,
RA Leer R., Tarchini R., Peters S.A., Sandbrink H.M., Fiers M.W.E.J.,
RA Stiekema W., Klein Lankhorst R.M., Bron P.A., Hoffer S.M.,
RA Nierop Groot M.N., Kerkhoven R., De Vries M., Ursing B., De Vos W.M.,
RA Siezen R.J.;
RT "Complete genome sequence of Lactobacillus plantarum WCFS1.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:1990-1995(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=22156394; DOI=10.1128/jb.06275-11;
RA Siezen R.J., Francke C., Renckens B., Boekhorst J., Wels M.,
RA Kleerebezem M., van Hijum S.A.;
RT "Complete resequencing and reannotation of the Lactobacillus plantarum
RT WCFS1 genome.";
RL J. Bacteriol. 194:195-196(2012).
RN [3]
RP INDUCTION.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=16166538; DOI=10.1128/jb.187.19.6750-6761.2005;
RA Goffin P., Deghorain M., Mainardi J.L., Tytgat I., Champomier-Verges M.C.,
RA Kleerebezem M., Hols P.;
RT "Lactate racemization as a rescue pathway for supplying D-lactate to the
RT cell wall biosynthesis machinery in Lactobacillus plantarum.";
RL J. Bacteriol. 187:6750-6761(2005).
RN [4]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=24710389; DOI=10.1038/ncomms4615;
RA Desguin B., Goffin P., Viaene E., Kleerebezem M., Martin-Diaconescu V.,
RA Maroney M.J., Declercq J.P., Soumillion P., Hols P.;
RT "Lactate racemase is a nickel-dependent enzyme activated by a widespread
RT maturation system.";
RL Nat. Commun. 5:3615-3615(2014).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, REACTION MECHANISM, ACTIVE SITE, MUTAGENESIS
RP OF ASP-30 AND CYS-176, AND DIDEHYDROALANINE FORMATION AT CYS-176.
RX PubMed=27114550; DOI=10.1073/pnas.1600486113;
RA Desguin B., Soumillion P., Hols P., Hausinger R.P.;
RT "Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium
RT carboxylation and LarE-dependent sacrificial sulfur insertion.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:5598-5603(2016).
CC -!- FUNCTION: Involved in the biosynthesis of a nickel-pincer cofactor
CC ((SCS)Ni(II) pincer complex). Catalyzes the ATP-dependent incorporation
CC of two sulfur atoms in pyridinium-3,5-biscarboxylic acid mononucleotide
CC (P2CMN) to yield pyridinium-3,5-bisthiocarboxylic acid mononucleotide
CC (P2TMN). The source of sulfur is the enzyme itself: Cys-176 of LarE is
CC the sulfur donor, thereby being converted into dehydroalanine, and is
CC not regenerated in vivo. Thus, two molecules of LarE undergo
CC sacrificial sulfur transfer to create one P2TMN (PubMed:27114550).
CC Binds nickel (PubMed:24710389). Is required for the activation of the
CC lactate racemase LarA (PubMed:24710389). May also be involved in the
CC activation of other nickel-pincer cofactor-dependent enzymes
CC (PubMed:27114550). {ECO:0000269|PubMed:24710389,
CC ECO:0000269|PubMed:27114550}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[LarE protein]-L-cysteine + ATP + pyridinium-3,5-dicarboxylate
CC mononucleotide = [LarE protein]-dehydroalanine + AMP + diphosphate +
CC H(+) + pyridinium-3-carboxylate-5-thiocarboxylate mononucleotide;
CC Xref=Rhea:RHEA:54788, Rhea:RHEA-COMP:13982, Rhea:RHEA-COMP:13985,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:90873, ChEBI:CHEBI:137353,
CC ChEBI:CHEBI:138330, ChEBI:CHEBI:456215; EC=4.4.1.37;
CC Evidence={ECO:0000269|PubMed:27114550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[LarE protein]-L-cysteine + ATP + pyridinium-3-carboxylate-5-
CC thiocarboxylate mononucleotide = [LarE protein]-dehydroalanine + AMP
CC + diphosphate + H(+) + pyridinium-3,5-bisthiocarboxylate
CC mononucleotide; Xref=Rhea:RHEA:54892, Rhea:RHEA-COMP:13982,
CC Rhea:RHEA-COMP:13985, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:90873,
CC ChEBI:CHEBI:137372, ChEBI:CHEBI:138330, ChEBI:CHEBI:456215;
CC EC=4.4.1.37; Evidence={ECO:0000269|PubMed:27114550};
CC -!- INDUCTION: Induced by L-lactate and repressed by D-lactate. Is thus
CC regulated by the L-lactate/D-lactate ratio. Makes part of the lar
CC operon (larABCDE). {ECO:0000269|PubMed:16166538,
CC ECO:0000269|PubMed:24710389}.
CC -!- DISRUPTION PHENOTYPE: Deletion of this gene leads to a loss of lactate
CC racemase activity. {ECO:0000269|PubMed:24710389}.
CC -!- SIMILARITY: Belongs to the LarE family. {ECO:0000305}.
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DR EMBL; AL935263; CCC77665.1; -; Genomic_DNA.
DR RefSeq; WP_003641716.1; NC_004567.2.
DR RefSeq; YP_004888179.1; NC_004567.2.
DR PDB; 5UDQ; X-ray; 2.09 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDR; X-ray; 2.62 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDS; X-ray; 2.37 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDT; X-ray; 3.19 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDU; X-ray; 2.79 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDV; X-ray; 2.62 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDW; X-ray; 2.70 A; A/B/C/D/E/F=1-276.
DR PDB; 5UDX; X-ray; 2.78 A; A/B/C/D/E/F=1-276.
DR PDB; 5UNM; X-ray; 2.58 A; A/B/C/D/E/F=1-276.
DR PDB; 6B2M; X-ray; 2.09 A; A/B/C/D/E/F=1-276.
DR PDB; 6B2O; X-ray; 2.35 A; A/B/C/D/E/F=1-276.
DR PDB; 6DG3; X-ray; 2.94 A; A/B/C/D/E/F/G/H/I/J/K/L=1-276.
DR PDB; 6UTP; X-ray; 3.55 A; A/B/C/D/E/F=1-276.
DR PDB; 6UTQ; X-ray; 2.39 A; A/B/C/D/E/F=1-276.
DR PDB; 6UTR; X-ray; 2.41 A; A/B/C/D/E/F=1-276.
DR PDB; 6UTT; X-ray; 2.49 A; A/B/C/D/E/F=1-276.
DR PDBsum; 5UDQ; -.
DR PDBsum; 5UDR; -.
DR PDBsum; 5UDS; -.
DR PDBsum; 5UDT; -.
DR PDBsum; 5UDU; -.
DR PDBsum; 5UDV; -.
DR PDBsum; 5UDW; -.
DR PDBsum; 5UDX; -.
DR PDBsum; 5UNM; -.
DR PDBsum; 6B2M; -.
DR PDBsum; 6B2O; -.
DR PDBsum; 6DG3; -.
DR PDBsum; 6UTP; -.
DR PDBsum; 6UTQ; -.
DR PDBsum; 6UTR; -.
DR PDBsum; 6UTT; -.
DR AlphaFoldDB; F9UST4; -.
DR SMR; F9UST4; -.
DR STRING; 220668.lp_0109; -.
DR DNASU; 1061362; -.
DR EnsemblBacteria; CCC77665; CCC77665; lp_0109.
DR GeneID; 57026951; -.
DR GeneID; 66448249; -.
DR KEGG; lpl:lp_0109; -.
DR PATRIC; fig|220668.9.peg.89; -.
DR eggNOG; COG1606; Bacteria.
DR HOGENOM; CLU_061181_2_0_9; -.
DR OMA; DKPAQPC; -.
DR PhylomeDB; F9UST4; -.
DR BioCyc; LPLA220668:G1GW0-87-MON; -.
DR BioCyc; MetaCyc:MON-20306; -.
DR BRENDA; 4.4.1.37; 2849.
DR Proteomes; UP000000432; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0016783; F:sulfurtransferase activity; IEA:InterPro.
DR CDD; cd01990; Alpha_ANH_like_I; 1.
DR DisProt; DP01168; -.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR005232; LarE.
DR InterPro; IPR022310; NAD/GMP_synthase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR43169:SF2; PTHR43169:SF2; 1.
DR Pfam; PF02540; NAD_synthase; 1.
DR PIRSF; PIRSF006661; PP-lp_UCP006661; 1.
DR TIGRFAMs; TIGR00268; TIGR00268; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Lyase; Nickel; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..276
FT /note="Pyridinium-3,5-bisthiocarboxylic acid mononucleotide
FT synthase"
FT /id="PRO_0000441655"
FT ACT_SITE 176
FT /note="Nucleophile and sulfur donor"
FT /evidence="ECO:0000269|PubMed:27114550"
FT MOD_RES 176
FT /note="2,3-didehydroalanine (Cys)"
FT /evidence="ECO:0000269|PubMed:27114550"
FT MUTAGEN 30
FT /note="D->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27114550"
FT MUTAGEN 176
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:27114550"
FT HELIX 4..18
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 20..24
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 29..42
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 47..53
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 59..72
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 87..90
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 96..115
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:5UDT"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:5UNM"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:5UDW"
FT HELIX 138..142
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 190..205
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 212..216
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 233..235
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:6B2M"
FT STRAND 249..254
FT /evidence="ECO:0007829|PDB:6B2M"
FT TURN 258..263
FT /evidence="ECO:0007829|PDB:6B2M"
FT HELIX 266..276
FT /evidence="ECO:0007829|PDB:6B2M"
SQ SEQUENCE 276 AA; 30484 MW; 94B4C899BBAD22EE CRC64;
MATLATKKAT LVAALKDLQR VTVAFSGGID STLVLKMALD VLGRDNVTAV VANSELFTDE
EFDKAMSLAE ELGANVQGTT LDYLSDDHIK NNTPDSWYYA KKMFYSRLND IAANNGSAAV
LDGMIKNDEN DYRPGLKARS EAGARSLLQE ADFFKTDVRA LAQELGLTNW NKVASCSVSS
RFPYGTTLTH DNIAQVMAAE KYLRSLGFPT VRVRFHNDIA RIELPEARIG DFLVFNDRVN
RQLQSLGFRY VTLDLGGFRS GRMNDTLTKA QLATFA
