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Literature summary extracted from

  • Gisselberg, J.E.; Herrera, Z.; Orchard, L.M.; Llinas, M.; Yeh, E.
    Specific inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase in Malaria parasites via a new small-molecule binding site (2018), Cell Chem. Biol., 25, 185-193 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
2.5.1.10 s228T inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase by MMV019313, but not bisphosphonates, is disrupted in an S228T variant Plasmodium falciparum
2.5.1.29 s228T inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase by MMV019313, but not bisphosphonates, is disrupted in an S228T variant Plasmodium falciparum

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.10 MMV019313 the inhibitor is highly selective for Plasmodium falciparum FPPS/GGPPS and shows no activity against human farnesyl diphosphate synthase or geranylgeranyl diphosphate synthase. Inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase by MMV019313, but not bisphosphonates, is disrupted in an S228T variant, demonstrating that MMV019313 and bisphosphonates have distinct modes-of-inhibition. Inhibition occurs via a new small molecule binding site Plasmodium falciparum
2.5.1.29 MMV019313 the inhibitor is highly selective for Plasmodium falciparum FPPS/GGPPS and shows no activity against human farnesyl diphosphate synthase or geranylgeranyl diphosphate synthase. Inhibition of the bifunctional farnesyl/geranylgeranyl diphosphate synthase by MMV019313, but not bisphosphonates, is disrupted in an S228T variant, demonstrating that MMV019313 and bisphosphonates have distinct modes-of-inhibition. Inhibition occurs via a new small molecule binding site Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.10 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate Plasmodium falciparum reaction of EC 2.5.1.29, bifunctional farnesyl/geranylgeranyl diphosphate synthase diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.10 geranyl diphosphate + isopentenyl diphosphate Plasmodium falciparum bifunctional farnesyl/geranylgeranyl diphosphate synthase diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?
2.5.1.29 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate Plasmodium falciparum bifunctional farnesyl/geranylgeranyl diphosphate synthase diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.29 geranyl diphosphate + isopentenyl diphosphate Plasmodium falciparum reaction of EC 2.5.1.10, bifunctional farnesyl/geranylgeranyl diphosphate synthase diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.10 Plasmodium falciparum Q8II79
-
-
2.5.1.29 Plasmodium falciparum Q8II79
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.10 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate reaction of EC 2.5.1.29, bifunctional farnesyl/geranylgeranyl diphosphate synthase Plasmodium falciparum diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.10 geranyl diphosphate + isopentenyl diphosphate bifunctional farnesyl/geranylgeranyl diphosphate synthase Plasmodium falciparum diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?
2.5.1.29 (2E,6E)-farnesyl diphosphate + isopentenyl diphosphate bifunctional farnesyl/geranylgeranyl diphosphate synthase Plasmodium falciparum diphosphate + geranylgeranyl diphosphate
-
 ?
2.5.1.29 geranyl diphosphate + isopentenyl diphosphate reaction of EC 2.5.1.10, bifunctional farnesyl/geranylgeranyl diphosphate synthase Plasmodium falciparum diphosphate + (2E,6E)-farnesyl diphosphate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.10 bifunctional farnesyl/geranylgeranyl diphosphate synthase
-
 Plasmodium falciparum
2.5.1.10 FPPS/GGPPS
-
 Plasmodium falciparum
2.5.1.29 bifunctional farnesyl/geranylgeranyl diphosphate synthase
-
 Plasmodium falciparum
2.5.1.29 FPPS/GGPPS
-
 Plasmodium falciparum

General Information

EC Number General Information Comment Organism
2.5.1.10 drug target antimalarial drug target Plasmodium falciparum
2.5.1.10 metabolism the bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis in Plasmodium falciparum (malaria) parasites Plasmodium falciparum
2.5.1.29 drug target antimalarial drug target Plasmodium falciparum
2.5.1.29 metabolism the bifunctional farnesyl/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is a key branchpoint enzyme in isoprenoid biosynthesis in Plasmodium falciparum (malaria) parasites Plasmodium falciparum