Trypanosoma rhodesiense: Mitochondrial proteins of bloodstream and procyclic trypomastigotes

Febvre, R B Le; Hill, George C.

doi:10.1016/0014-4894(86)90011-1

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…brucei, the parasitic agent of African sleeping sickness, is closely related to T. cruzi. Mitochondria of the BSF of T. brucei are largely repressed and are deficient in the complete set of Krebs cycle and oxidative phosphorylation enzymes (Nolan et al, 2000;Le Febvre & Hill, 1986). Thus, energy is mainly derived via the glycolytic pathway.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure of glycerol kinase from Trypanosoma cruzi, a potential molecular target in Chagas disease

Lipiński,

Sonani,

Dubin

2024

Acta Crystallogr D Struct Biol

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Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. It bears a significant global health burden with limited treatment options, thus calling for the development of new and effective drugs. Certain trypanosomal metabolic enzymes have been suggested to be druggable and valid for subsequent inhibition. In this study, the crystal structure of glycerol kinase from T. cruzi, a key enzyme in glycerol metabolism in this parasite, is presented. Structural analysis allowed a detailed description of the glycerol binding pocket, while comparative assessment pinpointed a potential regulatory site which may serve as a target for selective inhibition. These findings advance the understanding of glycerol metabolism in eukaryotes and provide a solid basis for the future treatment of Chagas disease.

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Section: Introductionmentioning

confidence: 99%

Crystal structure of glycerol kinase from Trypanosoma cruzi, a potential molecular target in Chagas disease

Lipiński,

Sonani,

Dubin

2024

Acta Crystallogr D Struct Biol

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“…The BSFs, unlike the PCFs and the host cells, contain a largely repressed mitochondrion that lacks the full complement of Krebs cycle and oxidative phosphorylation enzymes (Le Febvre and Hill, ; Nolan and Voorheis, ), hence, all their energy needs are derived from the glycolysis (Hannaert et al ., ). The glycolytic pathway of these parasites is compartmentalized within peroxisome‐like organelles called glycosomes.…”

Section: Introductionmentioning

confidence: 99%

Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase

Balogun

Inaoka

Shiba

et al. 2014

Molecular Microbiology

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SummaryThe glycerol kinase (GK) of African human trypanosomes is compartmentalized in their glycosomes. Unlike the host GK, which under physiological conditions catalyzes only the forward reaction (ATPdependent glycerol phosphorylation), trypanosome GK can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, GK is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure-based catalytic differences also contribute. To investigate this lack of information, the X-ray crystal structure of this protein was determined up to 1.90 Å resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure-guided mutagenesis suggests that the trypanosome GK is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non-conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome GK-specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s).

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Trypanosoma rhodesiense: Mitochondrial proteins of bloodstream and procyclic trypomastigotes

Cited by 2 publications

References 21 publications

Crystal structure of glycerol kinase from Trypanosoma cruzi, a potential molecular target in Chagas disease

Crystal structure of glycerol kinase from Trypanosoma cruzi, a potential molecular target in Chagas disease

Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase

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