| IED ID | IndEnz0018000929 |
| Enzyme Type ID | peroxidase000929 |
| Protein Name |
Dihydrolipoyl dehydrogenase LPD EC 1.8.1.4 Component of peroxynitrite reductase/peroxidase complex Component of PNR/P Dihydrolipoamide dehydrogenase E3 component of alpha-ketoacid dehydrogenase complexes |
| Gene Name | lpdC lpd Rv0462 MTV038.06 |
| Organism | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Taxonomic Lineage | cellular organisms Bacteria Terrabacteria group Actinobacteria Actinomycetia (high G+C Gram-positive bacteria) Corynebacteriales Mycobacteriaceae Mycobacterium Mycobacterium tuberculosis complex Mycobacterium tuberculosis Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Enzyme Sequence | MTHYDVVVLGAGPGGYVAAIRAAQLGLSTAIVEPKYWGGVCLNVGCIPSKALLRNAELVHIFTKDAKAFGISGEVTFDYGIAYDRSRKVAEGRVAGVHFLMKKNKITEIHGYGTFADANTLLVDLNDGGTESVTFDNAIIATGSSTRLVPGTSLSANVVTYEEQILSRELPKSIIIAGAGAIGMEFGYVLKNYGVDVTIVEFLPRALPNEDADVSKEIEKQFKKLGVTILTATKVESIADGGSQVTVTVTKDGVAQELKAEKVLQAIGFAPNVEGYGLDKAGVALTDRKAIGVDDYMRTNVGHIYAIGDVNGLLQLAHVAEAQGVVAAETIAGAETLTLGDHRMLPRATFCQPNVASFGLTEQQARNEGYDVVVAKFPFTANAKAHGVGDPSGFVKLVADAKHGELLGGHLVGHDVAELLPELTLAQRWDLTASELARNVHTHPTMSEALQECFHGLVGHMINF |
| Enzyme Length | 464 |
| Uniprot Accession Number | P9WHH9 |
| Absorption | |
| Active Site | ACT_SITE 443; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | ACTIVITY REGULATION: Triazaspirodimethoxybenzoyls are high-nanomolar inhibitors of M.tuberculosis Lpd and are non-competitive versus NADH, NAD(+), and lipoamide and >100-fold selective compared to human Lpd. {ECO:0000269|PubMed:20078138}. |
| Binding Site | BINDING 50; /note="FAD"; /evidence="ECO:0000269|PubMed:16093239, ECO:0000269|PubMed:20078138"; BINDING 113; /note="FAD; via amide nitrogen and carbonyl oxygen"; /evidence="ECO:0000250"; BINDING 201; /note="NAD"; /evidence="ECO:0000250"; BINDING 309; /note="FAD"; /evidence="ECO:0000269|PubMed:16093239, ECO:0000269|PubMed:20078138"; BINDING 317; /note="FAD; via amide nitrogen"; /evidence="ECO:0000269|PubMed:16093239, ECO:0000269|PubMed:20078138" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[protein] + NAD(+) = (R)-N(6)-lipoyl-L-lysyl-[protein] + H(+) + NADH; Xref=Rhea:RHEA:15045, Rhea:RHEA-COMP:10474, Rhea:RHEA-COMP:10475, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:83099, ChEBI:CHEBI:83100; EC=1.8.1.4; Evidence={ECO:0000269|PubMed:11560483}; |
| DNA Binding | |
| EC Number | 1.8.1.4 |
| Enzyme Function | FUNCTION: Lipoamide dehydrogenase is an essential component of the alpha-ketoacid dehydrogenase complexes, namely the pyruvate dehydrogenase (PDH) complex, the branched-chain alpha-ketoacid dehydrogenase (BCKADH) complex, and likely also the 2-oxoglutarate dehydrogenase (ODH) complex. Catalyzes the reoxidation of dihydrolipoyl groups which are covalently attached to the lipoate acyltransferase components (E2) of the complexes. Is also able to catalyze the transhydrogenation of NADH and thio-NAD(+) in the absence of D,L-lipoamide, and the NADH-dependent reduction of quinones in vitro.; FUNCTION: Together with AhpC, AhpD and DlaT, Lpd constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.; FUNCTION: Appears to be essential for Mtb pathogenesis. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.0 for PDH complex activity. Half-maximal activity is observed at pH 7.0 and pH 9.0. Activity is abolished at pH < 5. {ECO:0000269|PubMed:16045627}; |
| Pathway | |
| nucleotide Binding | NP_BIND 33..41; /note="FAD"; /evidence="ECO:0000269|PubMed:16093239, ECO:0000269|PubMed:20078138"; NP_BIND 178..182; /note="NAD"; /evidence="ECO:0000250"; NP_BIND 266..269; /note="NAD"; /evidence="ECO:0000250" |
| Features | Active site (1); Beta strand (24); Binding site (5); Chain (1); Disulfide bond (1); Helix (18); Mutagenesis (7); Nucleotide binding (3); Turn (2) |
| Keywords | 3D-structure;Antioxidant;Cytoplasm;Disulfide bond;FAD;Flavoprotein;Glycolysis;NAD;Oxidoreductase;Redox-active center;Reference proteome;Tricarboxylic acid cycle;Virulence |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (4) |
| Cross Reference PDB | 2A8X; 3II4; 4M52; 7KMY; |
| Mapped Pubmed ID | 24251446; |
| Motif | |
| Gene Encoded By | |
| Mass | 49,239 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=66 uM for NAD(+) {ECO:0000269|PubMed:11560483, ECO:0000269|PubMed:16045627}; KM=7.3 uM for NADH {ECO:0000269|PubMed:11560483, ECO:0000269|PubMed:16045627}; KM=110 uM for thio-NADH {ECO:0000269|PubMed:11560483, ECO:0000269|PubMed:16045627}; KM=16 mM for D,L-lipoamide {ECO:0000269|PubMed:11560483, ECO:0000269|PubMed:16045627}; KM=120 mM for D,L-lipoate {ECO:0000269|PubMed:11560483, ECO:0000269|PubMed:16045627}; |
| Metal Binding | |
| Rhea ID | RHEA:15045 |
| Cross Reference Brenda | 1.8.1.4; |