ArticleProceedings of the National Academy of Sciences of the United States of America2004
A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- Multiscale Process Modelling in Translational Systems Biology of Leishmania major: A Holistic view.Scientific reports · 2020Article
- Integrative Computational Framework for Understanding Metabolic Modulation in Leishmania.Frontiers in bioengineering and biotechnology · 2019Article
- Characteristic Variations and Similarities in Biochemical, Molecular, and Functional Properties of Glyoxalases across Prokaryotes and Eukaryotes.International journal of molecular sciences · 2017Review
- Nonredox nickel enzymes.Chemical reviews · 2014Review
- Structural variation in bacterial glyoxalase I enzymes: investigation of the metalloenzyme glyoxalase I from Clostridium acetobutylicum.The Journal of biological chemistry · 2011Article
- Methylglyoxal metabolism in trypanosomes and leishmania.Seminars in cell & developmental biology · 2011Review
- Drug resistance in leishmaniasis.Journal of global infectious diseases · 2010Article
- Drug targets in Leishmania.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2010Article
- Glyoxalase I gene deletion mutants of Leishmania donovani exhibit reduced methylglyoxal detoxification.PloS one · 2009Article
- A comparative study of methylglyoxal metabolism in trypanosomatids.The FEBS journal · 2009Article
- Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials.Antimicrobial agents and chemotherapy · 2008Article
- Phenotypic characterization of a glucose transporter null mutant in Leishmania mexicana.Molecular and biochemical parasitology · 2007Article
- Trypanothione-dependent glyoxalase I in Trypanosoma cruzi.The Biochemical journal · 2006Article
- Niche metabolism in parasitic protozoa.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2006Review
- Characterization of the gene encoding glyoxalase II from Leishmania donovani: a potential target for anti-parasite drugs.The Biochemical journal · 2006Article
- Phenotypic analysis of trypanothione synthetase knockdown in the African trypanosome.The Biochemical journal · 2005Article
- Crystallization and preliminary X-ray analysis of Leishmania major glyoxalase I.Acta crystallographica. Section F, Structural biology and crystallization communications · 2005Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Glyoxalase I forms part of the glyoxalase pathway that detoxifies reactive aldehydes such as methylglyoxal, using the spontaneously formed glutathione hemithioacetal as substrate. All known eukaryotic enzymes contain zinc as their metal cofactor, whereas the Escherichia coli glyoxalase I contains nickel. Database mining and sequence analysis identified putative glyoxalase I genes in the eukaryotic human parasites Leishmania major, Leishmania infantum, and Trypanosoma cruzi, with highest similarity to the cyanobacterial enzymes. Characterization of recombinant L. major glyoxalase I showed it to be unique among the eukaryotic enzymes in sharing the dependence of the E. coli enzyme on nickel. The parasite enzyme showed little activity with glutathione hemithioacetal substrates but was 200-fold more active with hemithioacetals formed from the unique trypanosomatid thiol trypanothione. L. major glyoxalase I also was insensitive to glutathione derivatives that are potent inhibitors of all other characterized glyoxalase I enzymes. This substrate specificity is distinct from that of the human enzyme and is reflected in the modification in the L. major sequence of a region of the human protein that interacts with the glycyl-carboxyl moiety of glutathione, a group that is conjugated to spermidine in trypanothione. This trypanothione-dependent glyoxalase I is therefore an attractive focus for additional biochemical and genetic investigation as a possible target for rational drug design.
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