LARA_LACPL
ID LARA_LACPL Reviewed; 424 AA.
AC F9USS9;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Lactate racemase {ECO:0000303|PubMed:24710389};
DE Short=Lar {ECO:0000303|PubMed:24710389};
DE EC=5.1.2.1 {ECO:0000269|PubMed:24710389, ECO:0000269|PubMed:26138974};
DE AltName: Full=Lactate racemization operon protein LarA {ECO:0000303|PubMed:16166538, ECO:0000312|EMBL:CCC77660.1};
GN Name=larA {ECO:0000303|PubMed:16166538, ECO:0000312|EMBL:CCC77660.1};
GN OrderedLocusNames=lp_0104 {ECO:0000312|EMBL:CCC77660.1};
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 FUNCTION, AND 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, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, 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 INDUCTION.
RC STRAIN=ATCC BAA-793 / NCIMB 8826 / WCFS1;
RX PubMed=25349156; DOI=10.1128/jb.02192-14;
RA Desguin B., Goffin P., Bakouche N., Diman A., Viaene E., Dandoy D.,
RA Fontaine L., Hallet B., Hols P.;
RT "Enantioselective regulation of lactate racemization by LarR in
RT Lactobacillus plantarum.";
RL J. Bacteriol. 197:219-230(2015).
RN [6]
RP ACTIVITY REGULATION, AND COFACTOR.
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-424 IN COMPLEX WITH (SCS)NI
RP COFACTOR, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP MUTAGENESIS OF ASP-72; ARG-75; HIS-108; HIS-174; LYS-184; HIS-200; GLN-295
RP AND LYS-298, REACTION MECHANISM, AND ACTIVE SITE.
RX PubMed=26138974; DOI=10.1126/science.aab2272;
RA Desguin B., Zhang T., Soumillion P., Hols P., Hu J., Hausinger R.P.;
RT "METALLOPROTEINS. A tethered niacin-derived pincer complex with a nickel-
RT carbon bond in lactate racemase.";
RL Science 349:66-69(2015).
CC -!- FUNCTION: Catalyzes the interconversion between the D- and L-isomers of
CC lactate (PubMed:24710389, PubMed:26138974). May act as a rescue enzyme
CC to ensure D-lactate production in physiological conditions where its
CC production by the D-lactate dehydrogenase LdhD is not sufficient
CC (PubMed:16166538). D-Lactate is absolutely required for growth of
CC L.plantarum and is an essential component of the cell wall
CC peptidoglycan in this species, where it is incorporated as the last
CC residue of the muramoyl-pentadepsipeptide peptidoglycan precursor; its
CC incorporation confers high level of vancomycin resistance
CC (PubMed:16166538). {ECO:0000269|PubMed:16166538,
CC ECO:0000269|PubMed:24710389, ECO:0000269|PubMed:26138974}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate = (R)-lactate; Xref=Rhea:RHEA:10960,
CC ChEBI:CHEBI:16004, ChEBI:CHEBI:16651; EC=5.1.2.1;
CC Evidence={ECO:0000269|PubMed:24710389, ECO:0000269|PubMed:26138974};
CC -!- COFACTOR:
CC Name=Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide;
CC Xref=ChEBI:CHEBI:137373; Evidence={ECO:0000269|PubMed:26138974};
CC Note=Was originally shown to use Ni(2+) as a cofactor
CC (PubMed:24710389), but in fact, the cofactor is a (SCS)Ni pincer
CC complex, a nicotinic acid mononucleotide derivative that is covalently
CC attached to Lys-184 and forms a tridentate pincer complex that
CC coordinates nickel through one metal-carbon and two metal-sulfur bonds
CC (PubMed:26138974, PubMed:27114550). {ECO:0000269|PubMed:24710389,
CC ECO:0000269|PubMed:26138974, ECO:0000269|PubMed:27114550};
CC -!- ACTIVITY REGULATION: Activation of the apo-enzyme requires the three
CC accessory proteins LarB, LarE and LarC, that are involved in the
CC biosynthesis of the nickel-pincer cofactor of LarA (PubMed:24710389,
CC PubMed:27114550). Inhibited by sulfite that behaves as a mixed
CC inhibitor (PubMed:26138974). {ECO:0000269|PubMed:24710389,
CC ECO:0000269|PubMed:26138974, ECO:0000269|PubMed:27114550}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=46 mM for L-lactate {ECO:0000269|PubMed:24710389};
CC KM=11 mM for D-lactate {ECO:0000269|PubMed:24710389};
CC Note=kcat is 4745 sec(-1) for conversion of L-lactate to D-lactate.
CC kcat is 1333 sec(-1) for conversion of D-lactate to L-lactate.
CC {ECO:0000269|PubMed:24710389};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:D9TQ02}.
CC -!- INDUCTION: Induced by L-lactate and repressed by D-lactate. The lactate
CC racemase activity is thus regulated by the L-lactate/D-lactate ratio,
CC under the control of the transcriptional regulator LarR. Makes part of
CC the lar operon (larABCDE). {ECO:0000269|PubMed:16166538,
CC ECO:0000269|PubMed:24710389, ECO:0000269|PubMed:25349156}.
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 lactate racemase family. {ECO:0000305}.
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DR EMBL; AL935263; CCC77660.1; -; Genomic_DNA.
DR RefSeq; WP_011100883.1; NC_004567.2.
DR RefSeq; YP_004888174.1; NC_004567.2.
DR PDB; 5HUQ; X-ray; 3.00 A; A/B=2-424.
DR PDB; 6C1W; X-ray; 2.40 A; A/B/C=1-424.
DR PDBsum; 5HUQ; -.
DR PDBsum; 6C1W; -.
DR AlphaFoldDB; F9USS9; -.
DR SMR; F9USS9; -.
DR STRING; 220668.lp_0104; -.
DR DNASU; 1061369; -.
DR EnsemblBacteria; CCC77660; CCC77660; lp_0104.
DR KEGG; lpl:lp_0104; -.
DR PATRIC; fig|220668.9.peg.84; -.
DR eggNOG; COG3875; Bacteria.
DR HOGENOM; CLU_050189_0_0_9; -.
DR OMA; GSVEPHY; -.
DR PhylomeDB; F9USS9; -.
DR BioCyc; LPLA220668:G1GW0-82-MON; -.
DR BioCyc; MetaCyc:MON-19498; -.
DR BRENDA; 5.1.2.1; 2849.
DR Proteomes; UP000000432; Chromosome.
DR GO; GO:0050043; F:lactate racemase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR Gene3D; 3.90.226.30; -; 1.
DR InterPro; IPR043166; LarA-like_C.
DR InterPro; IPR018657; LarA-like_N.
DR Pfam; PF09861; Lar_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Metal-binding; Nickel; Reference proteome.
FT CHAIN 1..424
FT /note="Lactate racemase"
FT /id="PRO_0000441651"
FT ACT_SITE 108
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:26138974"
FT ACT_SITE 174
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:26138974"
FT BINDING 72..75
FT /ligand="Ni(II)-pyridinium-3,5-bisthiocarboxylate
FT mononucleotide"
FT /ligand_id="ChEBI:CHEBI:137373"
FT /evidence="ECO:0000269|PubMed:26138974"
FT BINDING 184
FT /ligand="Ni(II)-pyridinium-3,5-bisthiocarboxylate
FT mononucleotide"
FT /ligand_id="ChEBI:CHEBI:137373"
FT /note="covalent"
FT /evidence="ECO:0000269|PubMed:26138974,
FT ECO:0000269|PubMed:27114550"
FT BINDING 200
FT /ligand="Ni(II)-pyridinium-3,5-bisthiocarboxylate
FT mononucleotide"
FT /ligand_id="ChEBI:CHEBI:137373"
FT /ligand_part="Ni"
FT /ligand_part_id="ChEBI:CHEBI:28112"
FT /evidence="ECO:0000269|PubMed:26138974"
FT BINDING 295
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26138974"
FT BINDING 298
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:26138974"
FT MUTAGEN 72
FT /note="D->A: Shows residual catalytic activity in vivo."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 75
FT /note="R->A: Retains some catalytic activity in vitro.
FT Exhibits reduced Ni content."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 108
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 174
FT /note="H->A: Loss of catalytic activity. Exhibits reduced
FT Ni content."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 184
FT /note="K->A: Shows residual catalytic activity in vivo.
FT Loss of Ni binding."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 200
FT /note="H->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 295
FT /note="Q->A: Retains some catalytic activity in vitro.
FT Exhibits reduced Ni content."
FT /evidence="ECO:0000269|PubMed:26138974"
FT MUTAGEN 298
FT /note="K->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:26138974"
FT STRAND 2..8
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 11..17
FT /evidence="ECO:0007829|PDB:6C1W"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 22..25
FT /evidence="ECO:0007829|PDB:6C1W"
FT TURN 29..32
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 39..48
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 56..59
FT /evidence="ECO:0007829|PDB:6C1W"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 79..93
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 97..104
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 113..120
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 122..127
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 128..132
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:6C1W"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:5HUQ"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:6C1W"
FT TURN 186..190
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 193..199
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 219..230
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 233..241
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 247..254
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 257..270
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 277..283
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 293..306
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 307..316
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 326..333
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 338..347
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 357..369
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 370..375
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 381..386
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 390..394
FT /evidence="ECO:0007829|PDB:6C1W"
FT HELIX 395..406
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 412..414
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:6C1W"
FT STRAND 422..424
FT /evidence="ECO:0007829|PDB:6C1W"
SQ SEQUENCE 424 AA; 46239 MW; 063CD5E0D19710D5 CRC64;
MVAIDLPYDK RTITAQIDDE NYAGKLVSQA ATYHNKLSEQ ETVEKSLDNP IGSDKLEELA
RGKHNIVIIS SDHTRPVPSH IITPILLRRL RSVAPDARIR ILVATGFHRP STHEELVNKY
GEDIVNNEEI VMHVSTDDSS MVKIGQLPSG GDCIINKVAA EADLLISEGF IESHFFAGFS
GGRKSVLPGI ASYKTIMANH SGEFINSPKA RTGNLMHNSI HKDMVYAART AKLAFIINVV
LDEDKKIIGS FAGDMEAAHK VGCDFVKELS SVPAIDCDIA ISTNGGYPLD QNIYQAVKGM
TAAEATNKEG GTIIMVAGAR DGHGGEGFYH NLADVDDPKE FLDQAINTPR LKTIPDQWTA
QIFARILVHH HVIFVSDLVD PDLITNMHME LAKTLDEAME KAYAREGQAA KVTVIPDGLG
VIVK
