Any feedback?
Literature summary extracted from
- Structural characterization of acidic M17 leucine aminopeptidases from the TriTryps and evaluation of their role in nutrient starvation in Trypanosoma brucei (2017), mSphere, 2, e00226-17 .
Application
| EC Number | Application | Comment | Organism |
|---|---|---|---|
| 3.4.11.1 | drug development | LAP-A as a potential drug target in Trypanosoma brucei | Trypanosoma brucei brucei |
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 3.4.11.1 | gene lap, recombinant expression of His-tagged enzyme in Escherichia coli | Leishmania major |
| 3.4.11.1 | gene lap, recombinant expression of His-tagged enzyme in Escherichia coli | Trypanosoma cruzi marinkellei |
| 3.4.11.1 | gene lap, recombinant expression of His-tagged enzyme in Escherichia coli, overexpression of c-Myc-tagged LAP-A in Trypanosoma brucei parasites cytosol | Trypanosoma brucei brucei |
Crystallization (Commentary)
| EC Number | Crystallization (Comment) | Organism |
|---|---|---|
| 3.4.11.1 | purified recombinant His-tagged enzyme LmLAP-A, in the presence of Mn2+, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement, modelling | Leishmania major |
| 3.4.11.1 | purified recombinant His-tagged enzyme LmLAP-A, X-ray diffraction structure determination and analysis at 2.5 A resolution, molecular replacement, modelling. TcLAP-A crystallizes exclusively under citratecontaining conditions, which leads to the absence of one or both Mn2x02 ions from the active site and hence no electron density for the inhibitors | Trypanosoma cruzi marinkellei |
| 3.4.11.1 | purified recombinant His-tagged enzyme TbLAP-A in complex with inhibitor bestatin, in the presence of ZnCl2 and Mn2+, X-ray diffraction structure determination and analysis, molecular replacement, modelling | Trypanosoma brucei brucei |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 3.4.11.1 | additional information | RNA interference (RNAi), double knockout (dKO), and overexpression of the protein in bloodstream form (BF) and procyclic form (PF) Trypanosoma brucei subsp. brucei parasites in culture. RNAi-mediated depletion of LAP-A, phenotype, overview | Trypanosoma brucei brucei |
| 3.4.11.1 | additional information | RNAi-mediated depletion of LAP-A, phenotype, overview | Leishmania major |
| 3.4.11.1 | additional information | RNAi-mediated depletion of LAP-A, phenotype, overview | Trypanosoma cruzi marinkellei |
Inhibitors
| EC Number | Inhibitors | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.11.1 | actinonin | 3-((1-((2-[hydroxymethyl]-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamoyl)octanohydroxaminic acid, actinonin in LmLAP-A is coordinated by the Mn2+ ions and hydrogen bonds | Leishmania major |  |
| 3.4.11.1 | actinonin | 3-((1-((2-[hydroxymethyl]-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamoyl)octanohydroxaminic acid. Actinonin in TbLAP-A is coordinated by the Mn2+ ions and hydrogen bonds, overview | Trypanosoma brucei brucei | |
| 3.4.11.1 | actinonin | 3-((1-((2-[hydroxymethyl]-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamoyl)octanohydroxaminic acid | Trypanosoma cruzi marinkellei | |
| 3.4.11.1 | amastatin | - |
Trypanosoma cruzi marinkellei | |
| 3.4.11.1 | bestatin | - |
Trypanosoma brucei brucei | |
| 3.4.11.1 | additional information | the structures of LAP-A in its apo and holo forms and in complex with inhibitors are practically identical. The apo LmLAP-A structure shows a completely ordered active site independent of metal or ligand binding | Leishmania major | |
| 3.4.11.1 | additional information | the structures of LAP-A in its apo and holo forms and in complex with inhibitors are practically identical | Trypanosoma brucei brucei | |
| 3.4.11.1 | additional information | the structures of LAP-A in its apo and holo forms and in complex with inhibitors are practically identical. The apo TcLAP-A structure shows a completely ordered active site independent of metal or ligand binding | Trypanosoma cruzi marinkellei |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 3.4.11.1 | cytoplasm | - |
Leishmania major | 5737 | - |
| 3.4.11.1 | cytoplasm | - |
Trypanosoma brucei brucei | 5737 | - |
| 3.4.11.1 | cytoplasm | - |
Trypanosoma cruzi marinkellei | 5737 | - |
| 3.4.11.1 | kinetoplast | - |
Leishmania major | 20023 | - |
| 3.4.11.1 | kinetoplast | - |
Trypanosoma brucei brucei | 20023 | - |
| 3.4.11.1 | kinetoplast | - |
Trypanosoma cruzi marinkellei | 20023 | - |
| 3.4.11.1 | additional information | in procyclic cells, LAP-A is equally distributed throughout the cytoplasm, yet upon starvation, it relocalizes in particles that concentrate in the perinuclear region. Effect of nutritional starvation on LAP-A subcellular localization | Leishmania major | - |
- |
| 3.4.11.1 | additional information | in procyclic cells, LAP-A is equally distributed throughout the cytoplasm, yet upon starvation, it relocalizes in particles that concentrate in the perinuclear region. Effect of nutritional starvation on LAP-A subcellular localization | Trypanosoma brucei brucei | - |
- |
| 3.4.11.1 | additional information | in procyclic cells, LAP-A is equally distributed throughout the cytoplasm, yet upon starvation, it relocalizes in particles that concentrate in the perinuclear region. Effect of nutritional starvation on LAP-A subcellular localization | Trypanosoma cruzi marinkellei | - |
- |
Metals/Ions
| EC Number | Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|---|
| 3.4.11.1 | Mn2+ | active site-bound | Leishmania major | |
| 3.4.11.1 | additional information | metalloprotease, metal coordination in the active site and apo LAP-A, overview | Leishmania major | |
| 3.4.11.1 | additional information | metalloprotease, metal coordination in the active site and apo LAP-A, overview | Trypanosoma cruzi marinkellei | |
| 3.4.11.1 | additional information | metalloprotease, metal coordination in the active site and apo LAP-A, overview. The metal-free apo TbLAP-A form shows a disordered active-site loop (aa 293 to 305) | Trypanosoma brucei brucei | |
| 3.4.11.1 | Zn2+ | required | Leishmania major | |
| 3.4.11.1 | Zn2+ | required | Trypanosoma brucei brucei | |
| 3.4.11.1 | Zn2+ | required | Trypanosoma cruzi marinkellei | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 3.4.11.1 | Leishmania major | Q7KF27 | - |
- |
| 3.4.11.1 | Trypanosoma brucei brucei | Q6Q833 | - |
- |
| 3.4.11.1 | Trypanosoma cruzi marinkellei | H2CS62 | - |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 3.4.11.1 | recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography and gel filtration | Leishmania major |
| 3.4.11.1 | recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography and gel filtration | Trypanosoma brucei brucei |
| 3.4.11.1 | recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography and gel filtration | Trypanosoma cruzi marinkellei |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 3.4.11.1 | L-Leu 7-amido-4-methylcoumarin + H2O | - |
Leishmania major | L-Leu + 7-amino-4-methylcoumarin | - |
? | |
| 3.4.11.1 | L-Leu 7-amido-4-methylcoumarin + H2O | - |
Trypanosoma brucei brucei | L-Leu + 7-amino-4-methylcoumarin | - |
? | |
| 3.4.11.1 | L-Leu 7-amido-4-methylcoumarin + H2O | - |
Trypanosoma cruzi marinkellei | L-Leu + 7-amino-4-methylcoumarin | - |
? | |
| 3.4.11.1 | additional information | little or no activity against L-Val 7-amido-4-methylcoumarin and L-Pro 7-amido-4-methylcoumarin is detected | Leishmania major | ? | - |
? | |
| 3.4.11.1 | additional information | little or no activity against L-Val 7-amido-4-methylcoumarin and L-Pro 7-amido-4-methylcoumarin is detected | Trypanosoma brucei brucei | ? | - |
? | |
| 3.4.11.1 | additional information | little or no activity against L-Val 7-amido-4-methylcoumarin and L-Pro 7-amido-4-methylcoumarin is detected | Trypanosoma cruzi marinkellei | ? | - |
? | |
Subunits
| EC Number | Subunits | Comment | Organism |
|---|---|---|---|
| 3.4.11.1 | homohexamer | - |
Leishmania major |
| 3.4.11.1 | homohexamer | - |
Trypanosoma brucei brucei |
| 3.4.11.1 | homohexamer | the hexamer is the most abundant species, while as the concentration was lowered, the proportion of trimers increases | Trypanosoma cruzi marinkellei |
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 3.4.11.1 | acidic M17 leucine aminopeptidase | - |
Leishmania major |
| 3.4.11.1 | acidic M17 leucine aminopeptidase | - |
Trypanosoma brucei brucei |
| 3.4.11.1 | acidic M17 leucine aminopeptidase | - |
Trypanosoma cruzi marinkellei |
| 3.4.11.1 | LAP-A | - |
Leishmania major |
| 3.4.11.1 | LAP-A | - |
Trypanosoma brucei brucei |
| 3.4.11.1 | LAP-A | - |
Trypanosoma cruzi marinkellei |
| 3.4.11.1 | leucine aminopeptidase | - |
Leishmania major |
| 3.4.11.1 | leucine aminopeptidase | - |
Trypanosoma brucei brucei |
| 3.4.11.1 | leucine aminopeptidase | - |
Trypanosoma cruzi marinkellei |
| 3.4.11.1 | LmLAP-A | - |
Leishmania major |
| 3.4.11.1 | TbLAP-A | - |
Trypanosoma brucei brucei |
| 3.4.11.1 | TcLAP-A | - |
Trypanosoma cruzi marinkellei |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 3.4.11.1 | evolution | the leucine aminopeptidase (LAP) is a member of the M17 family of metalloproteases | Leishmania major |
| 3.4.11.1 | evolution | the leucine aminopeptidase (LAP) is a member of the M17 family of metalloproteases | Trypanosoma brucei brucei |
| 3.4.11.1 | evolution | the leucine aminopeptidase (LAP) is a member of the M17 family of metalloproteases | Trypanosoma cruzi marinkellei |
| 3.4.11.1 | additional information | structure comparisons of plasmodial LAP-As from Trypanosoma brucei subsp. brucei, Trypanosoma cruzi, and Leishmania major, overview. Structural differences in LmLAP-A compared to TbLAP-A and TcLAP-A are mostly located in the loop regions | Leishmania major |
| 3.4.11.1 | additional information | structure comparisons of plasmodial LAP-As from Trypanosoma brucei subsp. brucei, Trypanosoma cruzi, and Leishmania major, overview. Structural differences in LmLAP-A compared to TbLAP-A and TcLAP-A are mostly located in the loop regions | Trypanosoma brucei brucei |
| 3.4.11.1 | additional information | structure comparisons of plasmodial LAP-As from Trypanosoma brucei subsp. brucei, Trypanosoma cruzi, and Leishmania major, overview. Structural differences in LmLAP-A compared to TbLAP-A and TcLAP-A are mostly located in the loop regions | Trypanosoma cruzi marinkellei |
| 3.4.11.1 | physiological function | the enzyme is not required for the growth of this parasite either in vitro or in vivo. Role of LAP-A in leucine starvation, overview | Leishmania major |
| 3.4.11.1 | physiological function | the enzyme is not required for the growth of this parasite either in vitro or in vivo. Role of LAP-A in leucine starvation, overview | Trypanosoma brucei brucei |
| 3.4.11.1 | physiological function | the enzyme is not required for the growth of this parasite either in vitro or in vivo. Role of LAP-A in leucine starvation, overview | Trypanosoma cruzi marinkellei |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
