Application | Comment | Organism |
---|---|---|
medicine | Leishmania arginase is a potential drug target for the treatment of leishmaniasis because this binuclear manganese metalloenzyme initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis. Polyamines such as spermidine are essential for the growth and survival of the parasite, so inhibition of enzymes in the polyamine-biosynthetic pathway comprises an effective strategy for treating parasitic infections | Leishmania mexicana |
Crystallization (Comment) | Organism |
---|---|
crystallization by sitting-drop vapor diffusion method at 21°C. Crystal structures of the enzyme complexed with alpha,alpha-disubstituted boronic amino-acid inhibitors | Leishmania mexicana |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(DL)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid | - |
Leishmania mexicana | |
(R)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid | - |
Leishmania mexicana | |
(R)-2-amino-6-borono-2-[2-(piperidin-1-yl)ethyl]hexanoic acid | - |
Leishmania mexicana | |
(S)-2-amino-6-borono-2-[2-(piperidin-1-yl)ethyl]hexanoic acid | - |
Leishmania mexicana | |
2-(S)-amino-6-boronohexanoic acid | - |
Leishmania mexicana |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mn2+ | binuclear manganese metalloenzyme | Leishmania mexicana |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Leishmania mexicana | Q6TUJ5 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-arginine + H2O | - |
Leishmania mexicana | L-ornithine + urea | - |
? |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
0.0009 | - |
2-(S)-amino-6-boronohexanoic acid | pH 8.0, 21°C | Leishmania mexicana | |
0.0011 | - |
(DL)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid | pH 8.0, 21°C | Leishmania mexicana | |
0.0014 | - |
(S)-2-amino-6-borono-2-[2-(piperidin-1-yl)ethyl]hexanoic acid | pH 8.0, 21°C | Leishmania mexicana |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0013 | - |
pH 8.0, 21°C | Leishmania mexicana | 2-(S)-amino-6-boronohexanoic acid | |
0.0017 | - |
pH 8.0, 21°C | Leishmania mexicana | (DL)-2-amino-6-borono-2-[1-(3,4-dichlorobenzyl)piperidin-4-yl]-hexanoic acid | |
0.0021 | - |
pH 8.0, 21°C | Leishmania mexicana | (S)-2-amino-6-borono-2-[2-(piperidin-1-yl)ethyl]hexanoic acid |
General Information | Comment | Organism |
---|---|---|
metabolism | initiates de novo polyamine biosynthesis by catalyzing the hydrolysis of L-arginine to generate L-ornithine and urea. The product L-ornithine subsequently undergoes decarboxylation to yield putrescine, which in turn is utilized for spermidine biosynthesis | Leishmania mexicana |