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Plasmodium falciparum N-myristoyltransferase

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Target id: 2955

Nomenclature: Plasmodium falciparum N-myristoyltransferase

Abbreviated Name: PfNMT

Family: Other antimalarial targets

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 410 NMT glycylpeptide N-tetradecanoyltransferase
Gene and Protein Information Comments
The P. falciparum genome encodes a single NMT isoform that is 50% identical to, and shares key catalytic residues with, human NMT.
Previous and Unofficial Names Click here for help
glycylpeptide N-tetradecanoyltransferase | Myristoyl-CoA:protein N-myristoyltransferase | Peptide N-myristoyltransferase | PF14_0127
Database Links Click here for help
Alphafold
ChEMBL Target
PlasmoDB
UniProtKB

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 34c [PMID: 24641010] Small molecule or natural product Primary target of this compound Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Inhibition 8.1 pKi 1
pKi 8.1 (Ki 8x10-9 M) [1]
Description: Enzyme inhibition assay
Whole Organism Assay Data Linked to This Target
Key to terms and symbols Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference
IMP-1002 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 7.7 pEC50 2
pEC50 7.7 (EC50 2.04x10-8 M) SYBR Green incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
IMP-1002 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 7.5 pEC50 2
pEC50 7.5 (EC50 3.4x10-8 M) SYBR Green incorporation [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 34c [PMID: 24641010] Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 6.6 pEC50 1
pEC50 6.6 (EC50 2.32x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
DDD85646 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf Parasite growth inhibition assay - - 6.6 pEC50 3
pEC50 6.6 (EC50 2.5x10-7 M) SYBR Green assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 34c [PMID: 24641010] Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 6.5 pEC50 1
pEC50 6.5 (EC50 3.02x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 34c [PMID: 24641010] Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfK1 Parasite growth inhibition assay - - 6.5 pEC50 1
pEC50 6.5 (EC50 3.39x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 34c [PMID: 24641010] Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pb Parasite liver stage assay - - 6.4 pEC50 1
pEC50 6.4 (EC50 3.72x10-7 M) Luciferase bioluminescence assay to measure viability of exoerythrocytic forms (EEF) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
compound 34c [PMID: 24641010] Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 6.0 pEC50 1
pEC50 6.0 (EC50 9.16x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The enzyme N-myristoyltransferase (NMT) catalyses cotranslational transfer of myristic acid from myristoyl coenzyme A to an N-terminal glycine. Genetic essentiality and validation of P. falciparum N-myristoyltransferase (PfNMT) as a chemically tractable antimalarial drug target has been reported. Small molecule on-target inhibition of myristoylation disrupts the function of multiple specific downstream pathways, resulting in rapid cell death [1,3].

References

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1. Rackham MD, Brannigan JA, Rangachari K, Meister S, Wilkinson AJ, Holder AA, Leatherbarrow RJ, Tate EW. (2014) Design and synthesis of high affinity inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferases directed by ligand efficiency dependent lipophilicity (LELP). J Med Chem, 57 (6): 2773-88. [PMID:24641010]

2. Schlott AC, Mayclin S, Reers AR, Coburn-Flynn O, Bell AS, Green J, Knuepfer E, Charter D, Bonnert R, Campo B et al.. (2019) Structure-Guided Identification of Resistance Breaking Antimalarial N‑Myristoyltransferase Inhibitors. Cell Chem Biol, 26 (7): 991-1000.e7. [PMID:31080074]

3. Wright MH, Clough B, Rackham MD, Rangachari K, Brannigan JA, Grainger M, Moss DK, Bottrill AR, Heal WP, Broncel M et al.. (2014) Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach. Nat Chem, 6 (2): 112-21. [PMID:24451586]

How to cite this page

Other antimalarial targets: Plasmodium falciparum N-myristoyltransferase. Last modified on 29/03/2022. Accessed on 02/07/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2955.