F9USS9 · LARA_LACPL
- ProteinLactate racemase
- GenelarA
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids424 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the interconversion between the D- and L-isomers of lactate (PubMed:24710389, PubMed:26138974).
May act as a rescue enzyme to ensure D-lactate production in physiological conditions where its production by the D-lactate dehydrogenase LdhD is not sufficient (PubMed:16166538).
D-Lactate is absolutely required for growth of L.plantarum and is an essential component of the cell wall peptidoglycan in this species, where it is incorporated as the last residue of the muramoyl-pentadepsipeptide peptidoglycan precursor; its incorporation confers high level of vancomycin resistance (PubMed:16166538).
May act as a rescue enzyme to ensure D-lactate production in physiological conditions where its production by the D-lactate dehydrogenase LdhD is not sufficient (PubMed:16166538).
D-Lactate is absolutely required for growth of L.plantarum and is an essential component of the cell wall peptidoglycan in this species, where it is incorporated as the last residue of the muramoyl-pentadepsipeptide peptidoglycan precursor; its incorporation confers high level of vancomycin resistance (PubMed:16166538).
Catalytic activity
- (S)-lactate = (R)-lactate
Cofactor
Note: Was originally shown to use Ni2+ as a cofactor (PubMed:24710389), but in fact, the cofactor is a (SCS)Ni pincer complex, a nicotinic acid mononucleotide derivative that is covalently attached to Lys-184 and forms a tridentate pincer complex that coordinates nickel through one metal-carbon and two metal-sulfur bonds (PubMed:26138974, PubMed:27114550).
Activity regulation
Activation of the apo-enzyme requires the three accessory proteins LarB, LarE and LarC, that are involved in the biosynthesis of the nickel-pincer cofactor of LarA (PubMed:24710389, PubMed:27114550).
Inhibited by sulfite that behaves as a mixed inhibitor (PubMed:26138974).
Inhibited by sulfite that behaves as a mixed inhibitor (PubMed:26138974).
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
46 mM | L-lactate | |||||
11 mM | D-lactate |
kcat is 4745 sec-1 for conversion of L-lactate to D-lactate. kcat is 1333 sec-1 for conversion of D-lactate to L-lactate.
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 72-75 | Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide (UniProtKB | ChEBI) | ||||
Sequence: DHTR | ||||||
Active site | 108 | Proton donor/acceptor | ||||
Sequence: H | ||||||
Active site | 174 | Proton donor/acceptor | ||||
Sequence: H | ||||||
Binding site | 184 | Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide (UniProtKB | ChEBI); covalent | ||||
Sequence: K | ||||||
Binding site | 200 | Ni (UniProtKB | ChEBI) of Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 295 | substrate | ||||
Sequence: Q | ||||||
Binding site | 298 | substrate | ||||
Sequence: K |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | lactate racemase activity | |
Molecular Function | metal ion binding |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLactate racemase
- EC number
- Short namesLar
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Bacillota > Bacilli > Lactobacillales > Lactobacillaceae > Lactiplantibacillus
Accessions
- Primary accessionF9USS9
Proteomes
Phenotypes & Variants
Disruption phenotype
Deletion of this gene leads to a loss of lactate racemase activity.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 72 | Shows residual catalytic activity in vivo. | ||||
Sequence: D → A | ||||||
Mutagenesis | 75 | Retains some catalytic activity in vitro. Exhibits reduced Ni content. | ||||
Sequence: R → A | ||||||
Mutagenesis | 108 | Loss of catalytic activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 174 | Loss of catalytic activity. Exhibits reduced Ni content. | ||||
Sequence: H → A | ||||||
Mutagenesis | 184 | Shows residual catalytic activity in vivo. Loss of Ni binding. | ||||
Sequence: K → A | ||||||
Mutagenesis | 200 | Loss of catalytic activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 295 | Retains some catalytic activity in vitro. Exhibits reduced Ni content. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 298 | Loss of catalytic activity. | ||||
Sequence: K → A |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441651 | 1-424 | Lactate racemase | |||
Sequence: MVAIDLPYDKRTITAQIDDENYAGKLVSQAATYHNKLSEQETVEKSLDNPIGSDKLEELARGKHNIVIISSDHTRPVPSHIITPILLRRLRSVAPDARIRILVATGFHRPSTHEELVNKYGEDIVNNEEIVMHVSTDDSSMVKIGQLPSGGDCIINKVAAEADLLISEGFIESHFFAGFSGGRKSVLPGIASYKTIMANHSGEFINSPKARTGNLMHNSIHKDMVYAARTAKLAFIINVVLDEDKKIIGSFAGDMEAAHKVGCDFVKELSSVPAIDCDIAISTNGGYPLDQNIYQAVKGMTAAEATNKEGGTIIMVAGARDGHGGEGFYHNLADVDDPKEFLDQAINTPRLKTIPDQWTAQIFARILVHHHVIFVSDLVDPDLITNMHMELAKTLDEAMEKAYAREGQAAKVTVIPDGLGVIVK |
Expression
Induction
Induced by L-lactate and repressed by D-lactate. The lactate racemase activity is thus regulated by the L-lactate/D-lactate ratio, under the control of the transcriptional regulator LarR. Makes part of the lar operon (larABCDE).
Interaction
Structure
Sequence
- Sequence statusComplete
- Length424
- Mass (Da)46,239
- Last updated2011-10-19 v1
- Checksum063CD5E0D19710D5
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL935263 EMBL· GenBank· DDBJ | CCC77660.1 EMBL· GenBank· DDBJ | Genomic DNA |