EC Number | Application | Comment | Organism |
---|---|---|---|
1.4.1.1 | medicine | an Ald-specific inhibitor and respiration inhibitory antitubercular drugs, such as Q203 and BDQ, are likely to enable more efficient therapies for tuberculosis | Mycolicibacterium smegmatis |
1.4.1.1 | medicine | plausible application of Ald inhibitors for treatment of tuberculosis. An Ald-specific inhibitor and respiration inhibitory antitubercular drugs, such as Q203 and BDQ, are likely to enable more efficient therapies for tuberculosis | Mycobacterium tuberculosis |
EC Number | Cloned (Comment) | Organism |
---|---|---|
1.4.1.1 | gene ald, genetic organization of the aldR-ald loci and their flanking genes | Mycobacterium tuberculosis |
1.4.1.1 | gene ald, genetic organization of the aldR-ald loci and their flanking genes | Mycobacterium marinum |
1.4.1.1 | gene ald, genetic organization of the aldR-ald loci and their flanking genes | Mycolicibacterium smegmatis |
EC Number | Inhibitors | Comment | Organism | Structure |
---|---|---|---|---|
1.4.1.1 | 1-(isonicotinamido)-N2,N4-bis(benzo[d]thiazol-2-yl)azetidine-2,4-dicarboxamide | - |
Mycobacterium tuberculosis | |
1.4.1.1 | 2-ethyl-N-phenethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine | the molecule shows activity against nutrient-starved nonreplicating Mycobacterium tuberculosis, resulting in a 2.7 log reduction of bacterial loads at 0.010 mg/ml, and is shown to be more potent than the first-line antitubercular drugs, isoniazid and rifampicin, at the same dose. compound is cytotoxic | Mycobacterium tuberculosis | |
1.4.1.1 | 4-(furan-2-ylmethylene)-1-phenylpyrazolidine-3,5-dione | the compound exhibited potent antitubercular activity against log-phase cultures of Mycobacterium tuberculosis with a MIC of 0.0245 mM, but is found to be less active than the lead compound 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione (CD59). The compound is cytotoxic | Mycobacterium tuberculosis | |
1.4.1.1 | additional information | development and optimization of compounds that inhibits the enzyme and can act as anti-tuberculosis drug, overview | Mycobacterium tuberculosis |
EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|---|
1.4.1.1 | 0.009 | 0.098 | NADH | pH and temperature not specified in the publication | Mycobacterium tuberculosis | |
1.4.1.1 | 0.31 | - |
NAD+ | pH and temperature not specified in the publication | Mycobacterium tuberculosis | |
1.4.1.1 | 0.76 | 2.8 | pyruvate | pH and temperature not specified in the publication | Mycobacterium tuberculosis | |
1.4.1.1 | 14 | 16 | L-alanine | pH and temperature not specified in the publication | Mycobacterium tuberculosis | |
1.4.1.1 | 35 | 2900 | NH3 | pH and temperature not specified in the publication | Mycobacterium tuberculosis |
EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium tuberculosis | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium marinum | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycolicibacterium smegmatis | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium sp. HE5 | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium marinum ATCC BAA-535 | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycolicibacterium smegmatis ATCC 700084 | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium tuberculosis H37Rv | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycobacterium tuberculosis ATCC 25618 | - |
pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | Mycolicibacterium smegmatis mc(2)155 | - |
pyruvate + NH3 + NADH + H+ | - |
r |
EC Number | Organism | UniProt | Comment | Textmining |
---|---|---|---|---|
1.4.1.1 | Mycobacterium marinum | B2HKV6 | - |
- |
1.4.1.1 | Mycobacterium marinum ATCC BAA-535 | B2HKV6 | - |
- |
1.4.1.1 | Mycobacterium sp. HE5 | - |
- |
- |
1.4.1.1 | Mycobacterium tuberculosis | P9WQB1 | - |
- |
1.4.1.1 | Mycobacterium tuberculosis ATCC 25618 | P9WQB1 | - |
- |
1.4.1.1 | Mycobacterium tuberculosis H37Rv | P9WQB1 | - |
- |
1.4.1.1 | Mycolicibacterium smegmatis | A0QVQ8 | Mycobacterium smegmatis | - |
1.4.1.1 | Mycolicibacterium smegmatis ATCC 700084 | A0QVQ8 | Mycobacterium smegmatis | - |
1.4.1.1 | Mycolicibacterium smegmatis mc(2)155 | A0QVQ8 | Mycobacterium smegmatis | - |
1.4.1.1 | no activity in Mycobacterium africanum | - |
Mycobacterium africanum does not to produce Ald due to a frameshift mutation within the ald gene | - |
1.4.1.1 | no activity in Mycobacterium bovis | - |
Mycobacterium bovis does not to produce Ald due to a frameshift mutation within the ald gene | - |
1.4.1.1 | no activity in Mycobacterium microti | - |
Mycobacterium microti does not to produce Ald due to a frameshift mutation within the ald gene | - |
EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|---|
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycobacterium tuberculosis | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycolicibacterium smegmatis | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycobacterium sp. HE5 | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycolicibacterium smegmatis ATCC 700084 | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycobacterium tuberculosis H37Rv | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycobacterium tuberculosis ATCC 25618 | glycine + NAD+ | - |
ir | |
1.4.1.1 | glyoxylate + NH3 + NADH + H+ | the enzyme catalyzes the reductive amination of glyoxylate to glycine, but not the reverse reaction | Mycolicibacterium smegmatis mc(2)155 | glycine + NAD+ | - |
ir | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium tuberculosis | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium marinum | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycolicibacterium smegmatis | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium sp. HE5 | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium marinum ATCC BAA-535 | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycolicibacterium smegmatis ATCC 700084 | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium tuberculosis H37Rv | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycobacterium tuberculosis ATCC 25618 | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | L-alanine + H2O + NAD+ | - |
Mycolicibacterium smegmatis mc(2)155 | pyruvate + NH3 + NADH + H+ | - |
r | |
1.4.1.1 | additional information | Ald catalyzes the reductive amination reaction faster and more efficiently than the oxidative deamination reaction | Mycobacterium tuberculosis | ? | - |
- |
|
1.4.1.1 | additional information | Ald catalyzes the reductive amination reaction faster and more efficiently than the oxidative deamination reaction | Mycobacterium tuberculosis H37Rv | ? | - |
- |
|
1.4.1.1 | additional information | Ald catalyzes the reductive amination reaction faster and more efficiently than the oxidative deamination reaction | Mycobacterium tuberculosis ATCC 25618 | ? | - |
- |
EC Number | Subunits | Comment | Organism |
---|---|---|---|
1.4.1.1 | homohexamer | - |
Mycobacterium tuberculosis |
EC Number | Synonyms | Comment | Organism |
---|---|---|---|
1.4.1.1 | ALD | - |
Mycobacterium tuberculosis |
1.4.1.1 | ALD | - |
Mycobacterium marinum |
1.4.1.1 | ALD | - |
Mycolicibacterium smegmatis |
1.4.1.1 | ALD | - |
Mycobacterium sp. HE5 |
1.4.1.1 | NAD(H)-dependent L-alanine dehydrogenase | - |
Mycobacterium tuberculosis |
1.4.1.1 | NAD(H)-dependent L-alanine dehydrogenase | - |
Mycobacterium marinum |
1.4.1.1 | NAD(H)-dependent L-alanine dehydrogenase | - |
Mycolicibacterium smegmatis |
1.4.1.1 | NAD(H)-dependent L-alanine dehydrogenase | - |
Mycobacterium sp. HE5 |
EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|---|
1.4.1.1 | 7 | 7.5 | reductive amination | Mycobacterium tuberculosis |
1.4.1.1 | 10 | 11 | oxidative deamination | Mycobacterium tuberculosis |
EC Number | Cofactor | Comment | Organism | Structure |
---|---|---|---|---|
1.4.1.1 | NAD+ | - |
Mycobacterium tuberculosis | |
1.4.1.1 | NAD+ | - |
Mycobacterium marinum | |
1.4.1.1 | NAD+ | - |
Mycolicibacterium smegmatis | |
1.4.1.1 | NAD+ | - |
Mycobacterium sp. HE5 | |
1.4.1.1 | NADH | - |
Mycobacterium tuberculosis | |
1.4.1.1 | NADH | - |
Mycobacterium marinum | |
1.4.1.1 | NADH | - |
Mycolicibacterium smegmatis | |
1.4.1.1 | NADH | - |
Mycobacterium sp. HE5 |
EC Number | IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|---|
1.4.1.1 | 0.00182 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | 2-ethyl-N-phenethyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine | |
1.4.1.1 | 0.00383 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | 1-(isonicotinamido)-N2,N4-bis(benzo[d]thiazol-2-yl)azetidine-2,4-dicarboxamide | |
1.4.1.1 | 0.00814 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | 4-(furan-2-ylmethylene)-1-phenylpyrazolidine-3,5-dione |
EC Number | Organism | Comment | Expression |
---|---|---|---|
1.4.1.1 | Mycobacterium marinum | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview | additional information |
1.4.1.1 | Mycolicibacterium smegmatis | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview | additional information |
1.4.1.1 | Mycobacterium tuberculosis | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview. AldR exerts its regulatory effect on ald expression by binding AldR binding sites bearing a consensus sequence of GA/T-N2-NWW/WWN-N2-T/AC (W = A or T, /= or) in Mycobacterium tuberculosis. Three-dimensional structure of AldR and phylogenetic analysis of AldRs from mycobacteria | additional information |
1.4.1.1 | Mycobacterium marinum | expression of the ald gene is upregulated in Mycobacterium marinum during longterm granulomatous infection in its host | up |
1.4.1.1 | Mycolicibacterium smegmatis | hypoxic induction of ald, which is independent of the DevSR (DosSR) two-component system, a major regulatory system involved in oxygen and NO sensing in mycobacteria | up |
1.4.1.1 | Mycobacterium tuberculosis | hypoxic induction of ald, which is independent of the DevSR (DosSR) two-component system, a major regulatory system involved in oxygen and NO sensing in mycobacteria. Expression of the ald gene is upregulated in Mycobacterium tuberculosis under nutrient starvation and energy-limiting conditions. The enzyme is strongly induced by the nitric oxide (NO) donor diethylenetriamine/NO, and in vivo during initial lung infection in mice | up |
EC Number | General Information | Comment | Organism |
---|---|---|---|
1.4.1.1 | evolution | distribution of Alds in mycobacteria, phylogenetic analysis and tree, overview. Alds of slow-growing mycobacteria are mostly distinct from those of fast-growing mycobacteria | Mycobacterium sp. HE5 |
1.4.1.1 | evolution | distribution of Alds in mycobacteria, phylogenetic analysis and tree, overview. Alds of slow-growing mycobacteria are mostly distinct from those of fast-growing mycobacteria. Structure of Ald and phylogenetic relevance of mycobacterial Alds | Mycobacterium tuberculosis |
1.4.1.1 | evolution | distribution of Alds in mycobacteria, phylogenetic analysis and tree, overview. Alds of slow-growing mycobacteria are mostly distinct from those of fast-growing mycobacteria. Structure of Ald and phylogenetic relevance of mycobacterial Alds | Mycobacterium marinum |
1.4.1.1 | evolution | distribution of Alds in mycobacteria, phylogenetic analysis and tree, overview. Alds of slow-growing mycobacteria are mostly distinct from those of fast-growing mycobacteria. Structure of Ald and phylogenetic relevance of mycobacterial Alds | Mycolicibacterium smegmatis |
1.4.1.1 | malfunction | an ald mutant of Mycolicibacterium smegmatis is much more sensitive to the bcc1 complex inhibitor Q203 than the isogenic wild-type strain. Another ald mutant of Mycolicibacterium smegmatis reportedly displays decreased survival under oxygen depletion conditions compared with the wild-type strain. When Mycolicibacterium smegmatis strains are treated with KCN under aerobic conditions, expression of the ald gene in a bd quinol oxidase mutant strain of Mycolicibacterium smegmatis expressing only the aa3 cytochrome c oxidase as a terminal oxidase is more induced than that in the corresponding wild-type strain expressing both terminal oxidases. Reduced functionality of the ETC, rather than direct regulation of ald by an O2-sensing regulatory system, is most relevant to hypoxic induction of ald expression | Mycolicibacterium smegmatis |
1.4.1.1 | malfunction | the inactivation of ald in Mycobacterium tuberculosis confers a low level of DCS resistance. The mechanism underlying DCS resistance resulting from ald inactivation is suggested as follows: Mycobacterium tuberculosis strains lacking the functional Ald cannot convert L-alanine to pyruvate, resulting in an increase in cellular levels of L-alanine. As DCS is a competitive inhibitor of alanine racemase, inhibition of alanine racemase by DCS might be overcome by increased concentrations of L-alanine that is a substrate of alanine racemase | Mycobacterium tuberculosis |
1.4.1.1 | metabolism | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview | Mycobacterium tuberculosis |
1.4.1.1 | metabolism | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview | Mycobacterium marinum |
1.4.1.1 | metabolism | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview | Mycobacterium sp. HE5 |
1.4.1.1 | metabolism | regulation mechanism of ald expression by the AldR transcription factor in response to alanine availability, model for the regulation of ald expression by AldR, overview. AldR exerts its regulatory effect on ald expression by binding AldR binding sites (O1, O2, O3, and O4) bearing a consensus sequence of GA/T-N2-NWW/WWN-N2-T/AC (W = A or T; / = or) in both Mycolicibacterium smegmatis. Three-dimensional structure of AldR and phylogenetic analysis of AldRs from mycobacteria | Mycolicibacterium smegmatis |
1.4.1.1 | physiological function | enzyme Ald is implicated in resistance of Mycobacterium tuberculosis to the second-line drug D-cycloserine (DCS). DCS is known to inhibit two enzymes, alanine racemase and D-alanine-D-alanine ligase | Mycobacterium tuberculosis |
1.4.1.1 | physiological function | enzyme Ald is suggested to primarily play a biosynthetic role by catalyzing the reductive amination of pyruvate to alanine as judged by the very small Keq for the oxidative deamination reaction | Mycobacterium tuberculosis |
1.4.1.1 | physiological function | enzyme Ald seems to play a crucial role in the growth and survival of the organism under severe respiration-inhibitory conditions such as the inhibitory condition of both the bcc1-aa3 branch and bd quinol oxidase of the respiratory ETC | Mycolicibacterium smegmatis |