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Literature summary for 2.5.1.10 extracted from

  • Gadelha, A.P.R.; Brigagao, C.M.; da Silva, M.B.; Rodrigues, A.B.M.; Guimaraes, A.C.R.; Paiva, F.; de Souza, W.; Henriques, C.
    Insights about the structure of farnesyl diphosphate synthase (FPPS) and the activity of bisphosphonates on the proliferation and ultrastructure of Leishmania and Giardia (2020), Parasit. Vectors, 13, 168 .
    View publication on PubMedView publication on EuropePMC
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Organism

Organism UniProt Comment Textmining
Giardia intestinalis A8B433
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Giardia intestinalis ATCC 50803 A8B433
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Leishmania infantum E9AH04
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Source Tissue

Source Tissue Comment Organism Textmining
promastigote
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 Leishmania infantum
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trophozoite
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 Giardia intestinalis
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Synonyms

Synonyms Comment Organism
farnesyl diphosphate synthase
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 Leishmania infantum
farnesyl diphosphate synthase
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 Giardia intestinalis
FPPS
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 Leishmania infantum
FPPS
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 Giardia intestinalis

General Information

General Information Comment Organism
drug target farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway and a good candidate for drug design Leishmania infantum
drug target farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway and a good candidate for drug design Giardia intestinalis
evolution Giardia and Leishmania farnesyl diphosphate synthase enzymes are phylogenetically distant but display conserved protein signatures. The nitrogen-containing bisphosphonates effect on farnesyl diphosphate synthase is more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the farnesyl diphosphate synthase catalytic site Leishmania infantum
evolution Giardia and Leishmania farnesyl diphosphate synthase enzymes are phylogenetically distant but display conserved protein signatures. The nitrogen-containing bisphosphonates effect on farnesyl diphosphate synthase is more pronounced in Leishmania than Giardia. This might be due to general differences in metabolism and differences in the farnesyl diphosphate synthase catalytic site Giardia intestinalis
malfunction inhibition of the enzyme by nitrogen-containing bisphosphonates (N-BPs) can cause a shortage of geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which are intermediate metabolites involved in the regulation of cellular functions and homeostasis. A shortage of farnesyl diphosphate can cause failure in the isoprenylation of proteins as well as the nuclear lamina and Rab GTPases that are anchored in the intracellular region of the plasma membrane. The nuclear lamina and Rab GTPases interfere with the vesicular transport, endocytosis and exocytosis. Deficits in the synthesis of dolichol interfere with asparagine (N)-linked glycosylation that regulates numerous cellular activities such as glycoprotein quality control, intracellular trafficking and cell-cell communications (disorganization of intracellular membranes culminating in Leishmania apoptosis) Leishmania infantum
malfunction inhibition of the enzyme by nitrogen-containing bisphosphonates (N-BPs) can cause a shortage of geranyl diphosphate, farnesyl diphosphate and geranylgeranyl diphosphate, which are intermediate metabolites involved in the regulation of cellular functions and homeostasis. A shortage of farnesyl diphosphate can cause failure in the isoprenylation of proteins as well as the nuclear lamina and Rab GTPases that are anchored in the intracellular region of the plasma membrane. The nuclear lamina and Rab GTPases interfere with the vesicular transport, endocytosis and exocytosis. Deficits in the synthesis of dolichol interfere with asparagine (N)-linked glycosylation that regulates numerous cellular activities such as glycoprotein quality control, intracellular trafficking and cell-cell communications (disorganization of intracellular membranes culminating in Leishmania apoptosis) Giardia intestinalis
metabolism farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway Leishmania infantum
metabolism farnesyl diphosphate synthase is in a branching point in sterol metabolic pathways. It is a key enzyme in the mevalonate pathway Giardia intestinalis