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Literature summary for 4.4.1.5 extracted from
- Glyoxalase diversity in parasitic protists (2014), Biochem. Soc. Trans., 42, 473-478.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | the enzyme is a promising drug target, since the functional monomeric Glo1 from Plasmodium falciparum differs significantly from its human homologue | Plasmodium falciparum |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| additional information | tight-binding inhibitors are very potent against the recombinant enzyme | Plasmodium falciparum | |
| S-4-bromobenzylglutathionylspermidine | - |
Leishmania braziliensis |  |
| S-4-bromobenzylglutathionylspermidine | - |
Trypanosoma cruzi | |
KM Value [mM]
| KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | the monomeric enzyme has two different active sites with similar kcat values, but distinct Km values | Plasmodium falciparum |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| apicoplast | - |
Plasmodium falciparum | 20011 | - |
| cytosol | - |
Plasmodium falciparum | 5829 | - |
| cytosol | the enzyme is dual-targeted | Trypanosoma cruzi | 5829 | - |
| mitochondrion | the enzyme is dual-targeted | Trypanosoma cruzi | 5739 | - |
| additional information | the enzyme does not localize to glycosomes and has no peroxisome-targeting signal | Leishmania donovani | - |
- |
| additional information | the enzyme does not localize to glycosomes and has no peroxisome-targeting signal | Leishmania major | - |
- |
| additional information | the enzyme does not localize to glycosomes and has no peroxisome-targeting signal | Leishmania infantum | - |
- |
| additional information | the enzyme does not localize to glycosomes and has no peroxisome-targeting signal | Leishmania braziliensis | - |
- |
| additional information | the parasite genome encodes 2 glyoxalases I, a cytosolic isoform, and a Glo1-like protein that localizes to the apicoplast | Plasmodium falciparum | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Ni2+ | required | Trypanosoma cruzi | |
| Ni2+ | required | Leishmania major | |
| Zn2+ | required | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| glutathione + methylglyoxal | Homo sapiens | - |
(R)-S-lactoylglutathione | - |
? | |
| glutathione + methylglyoxal | Plasmodium falciparum | - |
(R)-S-lactoylglutathione | - |
? | |
| trypanothione + 2 methylglyoxal | Leishmania infantum | - |
5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | Leishmania donovani | - |
5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | Trypanosoma cruzi | - |
5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | Leishmania major | - |
5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | Leishmania braziliensis | - |
5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Leishmania braziliensis | - |
- |
- |
| Leishmania donovani | - |
- |
- |
| Leishmania infantum | - |
- |
- |
| Leishmania major | - |
- |
- |
| no activity in Entamoeba histolytica | - |
- |
- |
| no activity in Giardia lamblia | - |
- |
- |
| no activity in Trypanosoma brucei | - |
- |
- |
| Plasmodium falciparum | - |
- |
- |
| Trypanosoma cruzi | - |
- |
- |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| glutathione + methylglyoxal | - |
Homo sapiens | (R)-S-lactoylglutathione | - |
? | |
| glutathione + methylglyoxal | - |
Plasmodium falciparum | (R)-S-lactoylglutathione | - |
? | |
| glutathione + methylglyoxal | cytosolic isozyme Glo1 is functional, but the recombinant Glo1-like protein is inactive in a standard enzyme assay | Plasmodium falciparum | (R)-S-lactoylglutathione | - |
? | |
| trypanothione + 2 methylglyoxal | - |
Leishmania infantum | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + 2 methylglyoxal | high specificity of the kinetoplastid Glo1 isoform for its trypanothione, i.e. N1,N8-bis(glutathionyl)spermidine, substrate as compared with glutathione | Leishmania infantum | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | - |
Leishmania donovani | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | - |
Trypanosoma cruzi | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | - |
Leishmania major | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | - |
Leishmania braziliensis | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | high specificity of the kinetoplastid Glo1 isoform for its trypanothione, i.e. N1,N8-bis(glutathionyl)spermidine, substrate as compared with glutathione | Leishmania donovani | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | high specificity of the kinetoplastid Glo1 isoform for its trypanothione, i.e. N1,N8-bis(glutathionyl)spermidine, substrate as compared with glutathione | Trypanosoma cruzi | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | high specificity of the kinetoplastid Glo1 isoform for its trypanothione, i.e. N1,N8-bis(glutathionyl)spermidine, substrate as compared with glutathione | Leishmania major | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
| trypanothione + methylglyoxal | high specificity of the kinetoplastid Glo1 isoform for its trypanothione, i.e. N1,N8-bis(glutathionyl)spermidine, substrate as compared with glutathione | Leishmania braziliensis | 5,5'-bi((R)-lactoyl)trypanothione | - |
? | |
Subunits
| Subunits | Comment | Organism |
|---|---|---|
| homodimer | homodimeric enzyme with two structurally identical active sites | Homo sapiens |
| monomer | the monomeric enzyme has two different active sites with similar kcat values, but distinct Km values. Both active sites adopt two discrete conformations and are allosterically coupled in a substrate concentration-dependent manner | Plasmodium falciparum |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Glo1 | - |
Homo sapiens |
| Glo1 | - |
Leishmania donovani |
| Glo1 | - |
Trypanosoma cruzi |
| Glo1 | - |
Plasmodium falciparum |
| Glo1 | - |
Leishmania major |
| Glo1 | - |
Leishmania infantum |
| Glo1 | - |
Leishmania braziliensis |
| glyoxalase I | - |
Homo sapiens |
| glyoxalase I | - |
Leishmania donovani |
| glyoxalase I | - |
Trypanosoma cruzi |
| glyoxalase I | - |
Plasmodium falciparum |
| glyoxalase I | - |
Leishmania major |
| glyoxalase I | - |
Leishmania infantum |
| glyoxalase I | - |
Leishmania braziliensis |
Turnover Number [1/s]
| Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|
| additional information | - |
additional information | the monomeric enzyme has two different active sites with similar kcat values, but distinct Km values | Plasmodium falciparum |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0005 | - |
S-4-bromobenzylglutathionylspermidine | pH and temperature not specified in the publication | Leishmania braziliensis | |
| 0.005 | - |
S-4-bromobenzylglutathionylspermidine | pH and temperature not specified in the publication | Trypanosoma cruzi | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | evolutionary early prokaryotic gene transfer. The enzyme of kinetoplastid parasites has highly altered substrate-binding site due to the usage of trypanothione instead of glutathione. Trypanothione is entropically favoured in comparison with the formation of glutathione disulfide. In addition, trypanothione is more reactive because of a significantly lower thiol pKa value of 7.4, has an overall positive instead of negative charge and is much bulkier than GSH. Because of the spermidine moiety, the substrate-binding sites are partially neutral or negatively (instead of positively) charged, and the binding sites of kinetoplastid glyoxalases are much wider to accommodate the additional spermidine and second glutathione moiety | Leishmania donovani |
| evolution | evolutionary early prokaryotic gene transfer. The enzyme of kinetoplastid parasites has highly altered substrate-binding site due to the usage of trypanothione instead of glutathione. Trypanothione is entropically favoured in comparison with the formation of glutathione disulfide. In addition, trypanothione is more reactive because of a significantly lower thiol pKa value of 7.4, has an overall positive instead of negative charge and is much bulkier than GSH. Because of the spermidine moiety, the substrate-binding sites are partially neutral or negatively (instead of positively) charged, and the binding sites of kinetoplastid glyoxalases are much wider to accommodate the additional spermidine and second glutathione moiety | Trypanosoma cruzi |
| evolution | evolutionary early prokaryotic gene transfer. The enzyme of kinetoplastid parasites has highly altered substrate-binding site due to the usage of trypanothione instead of glutathione. Trypanothione is entropically favoured in comparison with the formation of glutathione disulfide. In addition, trypanothione is more reactive because of a significantly lower thiol pKa value of 7.4, has an overall positive instead of negative charge and is much bulkier than GSH. Because of the spermidine moiety, the substrate-binding sites are partially neutral or negatively (instead of positively) charged, and the binding sites of kinetoplastid glyoxalases are much wider to accommodate the additional spermidine and second glutathione moiety | Leishmania major |
| evolution | evolutionary early prokaryotic gene transfer. The enzyme of kinetoplastid parasites has highly altered substrate-binding site due to the usage of trypanothione instead of glutathione. Trypanothione is entropically favoured in comparison with the formation of glutathione disulfide. In addition, trypanothione is more reactive because of a significantly lower thiol pKa value of 7.4, has an overall positive instead of negative charge and is much bulkier than GSH. Because of the spermidine moiety, the substrate-binding sites are partially neutral or negatively (instead of positively) charged, and the binding sites of kinetoplastid glyoxalases are much wider to accommodate the additional spermidine and second glutathione moiety | Leishmania infantum |
| evolution | evolutionary early prokaryotic gene transfer. The enzyme of kinetoplastid parasites has highly altered substrate-binding site due to the usage of trypanothione instead of glutathione. Trypanothione is entropically favoured in comparison with the formation of glutathione disulfide. In addition, trypanothione is more reactive because of a significantly lower thiol pKa value of 7.4, has an overall positive instead of negative charge and is much bulkier than GSH. Because of the spermidine moiety, the substrate-binding sites are partially neutral or negatively (instead of positively) charged, and the binding sites of kinetoplastid glyoxalases are much wider to accommodate the additional spermidine and second glutathione moiety | Leishmania braziliensis |
| evolution | regarding the quaternary structure, the monomeric enzyme probably resulted from a second gene-duplication event in the course of evolution | Plasmodium falciparum |
| metabolism | the conversion of methylglyoxal into lactic acid depends on the isomerase Glo1 (glyoxalase I), the thioesterase Glo2 (glyoxalase II) and reduced glutathione (GSH) as a coenzyme, together they compose the glyoxalase system | Homo sapiens |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and glutathione | Plasmodium falciparum |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and trypanothione | Leishmania donovani |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and trypanothione | Trypanosoma cruzi |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and trypanothione | Leishmania major |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and trypanothione | Leishmania infantum |
| metabolism | the enzyme acts in a glyoxalase detoxification system with glyoxalase 2 and trypanothione | Leishmania braziliensis |
| metabolism | the enzyme acts in a system with glyoxalase 2 and glutathione. The allosteric regulation of the high-activity and the high-affinity conformation of the enzyme might be an adaptation to altered methylglyoxal fluxes | Plasmodium falciparum |
| physiological function | malaria parasites are expected to require a functional glyoxalase system to prevent the potentially toxic accumulation of methylglyoxal and advanced glycation end-products | Plasmodium falciparum |
| physiological function | the enzyme is essential and contributes to the detoxification of (exogenous) methylglyoxal | Leishmania donovani |
| physiological function | the enzyme is essential and contributes to the detoxification of (exogenous) methylglyoxal | Leishmania infantum |
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