{"gene":"PF3D7_1412800","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2000,"finding":"P. falciparum NMT (PF3D7_1412800) was cloned from P. falciparum, shown to be single-copy with mRNA expressed in asexual blood stages, and the recombinant protein expressed in E. coli was demonstrated to have myristoyltransferase enzymatic activity using a synthetic peptide substrate. The active-site residues important for substrate binding and catalysis in other species are conserved. Unlike human NMT, P. falciparum NMT activity was not inhibited by diethylpyrocarbonate or iodoacetamide, indicating a different pattern of inhibitor sensitivity by chemical modification.","method":"Gene cloning, cDNA/genomic sequence comparison, recombinant protein expression in E. coli, in vitro enzymatic activity assay with synthetic peptide substrate, chemical modification inhibition assays","journal":"The Biochemical journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzymatic reconstitution with mutagenesis-level chemical probing; single lab but multiple orthogonal methods (cloning, expression, activity assay, chemical inhibition comparison)","pmids":["10816442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"P. falciparum NMT (PF3D7_1412800) was co-expressed with adenylate kinase 2 (AK2) in E. coli in the presence of myristate, and mass spectrometry confirmed that NMT catalyzes myristoylation of the intact malarial AK2 protein. Furthermore, AK2 and NMT were shown to interact strongly with each other, forming a heterodimeric protein complex in vitro.","method":"Heterologous co-expression in E. coli, protein purification, mass spectrometry for myristoylation confirmation, in vitro protein-protein interaction (heterodimer formation)","journal":"Molecular and biochemical parasitology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of myristoylation confirmed by mass spectrometry, plus direct protein-protein interaction shown; single lab, two orthogonal methods","pmids":["18973776"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Tetracycline-induced conditional knockdown of N-myristoyltransferase (NMT) in P. berghei using a TetR-based transactivator system resulted in a dramatic reduction in parasite viability, establishing that NMT is essential for P. berghei blood-stage parasite survival.","method":"Conditional knockdown using tetracycline-repressible transactivator (TetR) system, parasite viability assay","journal":"Cell host & microbe","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined viability phenotype in a genetic model; single lab but robust genetic system with clear phenotypic readout","pmids":["23245327"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2019,"finding":"ACBD6 (an acyl-CoA binding domain protein) supports and regulates the activity of P. falciparum NMT (PF3D7_1412800). ACBD6 protects NMT from inhibition by lauryl-CoA and promotes preferential use of myristoyl-CoA substrate, thereby enhancing N-myristoylation under substrate-limiting conditions where palmitoyl-CoA competes with myristoyl-CoA for NMT binding.","method":"In vitro enzymatic activity assays with recombinant proteins, acyl-CoA competition assays","journal":"Journal of lipid research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — in vitro functional reconstitution with defined substrate competition, single lab, single method set","pmids":["30642881"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Treatment of P. falciparum with NMT inhibitor IMP-1002 during schizogony blocked parasite egress from erythrocytes, disrupted rhoptry protein localization, and impaired erythrocyte invasion. Sixteen NMT substrate proteins showed significantly reduced myristoylation upon NMTi treatment, of which six were substantially reduced in abundance. Replacement of the N-terminal glycine with alanine (preventing myristoylation) in four of these substrates substantially impaired parasite fitness. For GAP45 specifically, loss of myristoylation did not affect protein localization or glideosome assembly but was essential for erythrocyte invasion, demonstrating mechanistically distinct consequences of myristoylation for individual substrates. NMT inhibition thus disrupts parasite development at three stages: early schizogony (pseudoschizont formation), late schizogony (rhoptry formation/egress), and invasion.","method":"Chemical biology (NMT inhibitor treatment), genetic modification (N-terminal glycine-to-alanine substitution), parasite viability screen, chemical proteomics for myristoylation profiling, fluorescence microscopy for protein localization, parasite egress and invasion assays","journal":"PLoS biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (chemical inhibition, genetic mutation, chemical proteomics, functional assays) in a single rigorous study establishing pleiotropic mechanistic roles","pmids":["34695132"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"In vitro resistance to a specific NMT inhibitor series was mediated by a single amino acid substitution in the NMT substrate-binding pocket, validated by crystallography, enzyme activity assays, stability assays, and surface plasmon resonance. A second inhibitor series was identified that was unaffected by this substitution.","method":"In vitro resistance selection, crystallography, enzyme activity assays, thermal stability assays, surface plasmon resonance","journal":"Cell chemical biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus multiple orthogonal biochemical assays (SPR, enzyme kinetics, stability); single lab but multiple rigorous methods validating the resistance mechanism","pmids":["31080074"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"finding":"Crystal structure of P. vivax NMT in complex with a hit compound from high-throughput screening was obtained at high resolution, revealing the novel binding mode of the inhibitor in the NMT active site. Structure-activity relationships defined chemical groups relevant for activity and selectivity.","method":"High-throughput screening, X-ray crystallography (high-resolution co-crystal structure with inhibitor), structure-activity relationship analysis","journal":"Journal of medicinal chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure with functional (SAR) validation; single lab, two orthogonal methods","pmids":["22439843"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2014,"finding":"High-resolution crystal structures of peptidomimetic inhibitors in complex with P. falciparum NMT and Leishmania NMT were obtained, including the first crystal structure evidence for a ternary NMT–Coenzyme A/myristoylated peptide product complex, revealing comparative binding modes between Plasmodium and Leishmania NMTs.","method":"X-ray crystallography (ternary complex structure), enzyme inhibition assays","journal":"Organic & biomolecular chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure of ternary product complex providing direct mechanistic insight into the catalytic mechanism; single lab, structural and biochemical methods","pmids":["25230674"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"NMT inhibition in P. falciparum results in incorrect localization of myristoylated substrate proteins, disrupting their membrane interactions and causing pleiotropic effects on parasite development, growth, and multiplication. NMT substrates include proteins involved in secretory transport and apicomplexan-specific processes including gliding motility.","method":"Review/perspective synthesizing chemical biology and inhibitor studies; substrate localization experiments cited from prior work","journal":"ACS infectious diseases","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — synthesis of experimental evidence from multiple studies; mechanistic claim about mislocalization supported by referenced experimental data","pmids":["29363940"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"A 1.8 Å resolution ternary crystal structure of P. vivax NMT in complex with myristoyl-CoA and the inhibitor IMP-1088 was determined, showing that IMP-1088 binds PvNMT similarly to how it binds human NMT, occupying the peptide substrate-binding pocket.","method":"X-ray crystallography (1.8 Å ternary complex structure)","journal":"Acta crystallographica. Section F, Structural biology communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — high-resolution crystal structure of ternary complex with functional inhibitor; single lab, rigorous structural determination","pmids":["39655507"],"is_preprint":false,"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2006,"finding":"GAP45 in P. falciparum merozoites undergoes dual acylation: N-terminal myristoylation (catalyzed by NMT) and palmitoylation. This dual acylation is important for membrane association of GAP45.","method":"Metabolic labeling with [3H]-myristate and [3H]-palmitate, immunoprecipitation, mass spectrometry","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct biochemical demonstration of NMT-dependent myristoylation of a specific substrate; single lab, multiple labeling methods","pmids":["16750579"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum NMT (PF3D7_1412800) is a cytosolic, single-copy, essential myristoyltransferase that co-translationally transfers myristate from myristoyl-CoA to the N-terminal glycine of diverse substrate proteins (including GAP45, AK2, and rhoptry proteins); its activity is regulated by the acyl-CoA binding protein ACBD6 which enforces myristoyl-CoA specificity, it forms a heterodimer with substrate AK2 in vitro, and its inhibition causes pleiotropic disruption of parasite development at three distinct stages—early schizogony, late schizogony/egress, and erythrocyte invasion—primarily through mislocalization or destabilization of myristoylated substrates essential for membrane targeting and parasite motility."},"narrative":{"mechanistic_narrative":"PF3D7_1412800 (NMT) is a single-copy, essential glycylpeptide N-tetradecanoyltransferase of Plasmodium that transfers myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins during asexual blood-stage development [PMID:10816442, PMID:23245327]. The recombinant enzyme is catalytically active on synthetic peptide substrates, its catalytic and substrate-binding residues are conserved, and it displays a chemical-inhibitor sensitivity distinct from the human enzyme [PMID:10816442]. NMT myristoylates a defined set of parasite substrates including adenylate kinase 2 (AK2), with which it also forms a heterodimeric complex in vitro [PMID:18973776], and the glideosome protein GAP45, which is dually acylated by N-terminal myristoylation and palmitoylation to support membrane association [PMID:16750579]. Enzyme activity is regulated by the acyl-CoA binding protein ACBD6, which protects NMT from lauryl-CoA inhibition and enforces preferential use of myristoyl-CoA over competing palmitoyl-CoA [PMID:30642881]. Pharmacological inhibition disrupts parasite development at three stages—early schizogony, late schizogony/egress, and erythrocyte invasion—by reducing myristoylation and destabilizing or mislocalizing substrate proteins, with substrate-specific consequences: for GAP45, loss of myristoylation spares localization and glideosome assembly yet is still required for invasion [PMID:34695132, PMID:29363940]. High-resolution ternary crystal structures of Plasmodium NMTs capture the enzyme with myristoyl-CoA and peptidomimetic or drug-like inhibitors bound in the peptide-substrate pocket, and a single substitution in that pocket confers resistance to one inhibitor series, validating the active site as an antimalarial target [PMID:31080074, PMID:22439843, PMID:25230674, PMID:39655507].","teleology":[{"year":2000,"claim":"Establishing that Plasmodium encodes a genuine myristoyltransferase answered whether the parasite possesses this enzymatic machinery and whether its catalytic properties differ from the human host enzyme.","evidence":"Cloning, sequence comparison, recombinant expression in E. coli, in vitro activity assay on a synthetic peptide, and chemical-modification inhibition comparisons","pmids":["10816442"],"confidence":"High","gaps":["Endogenous substrate repertoire not defined","Subcellular localization in the parasite not established","Essentiality not yet tested genetically"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"Identifying GAP45 as a dually acylated NMT substrate connected the enzyme to a specific membrane-targeting event in merozoites.","evidence":"Metabolic labeling with [3H]-myristate and [3H]-palmitate, immunoprecipitation, and mass spectrometry in P. falciparum","pmids":["16750579"],"confidence":"Medium","gaps":["Functional requirement of GAP45 myristoylation for invasion not yet dissected here","Interplay of myristoylation and palmitoylation timing unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"claim":"Demonstrating myristoylation of intact AK2 and a stable NMT–AK2 heterodimer showed NMT acts on a full-length parasite protein and can form a defined complex with a substrate.","evidence":"Co-expression in E. coli with myristate, purification, mass spectrometry, and in vitro protein-protein interaction","pmids":["18973776"],"confidence":"High","gaps":["Physiological relevance of the heterodimer in vivo unknown","Whether heterodimerization reflects a general substrate-engagement mode or is AK2-specific is unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2012,"claim":"Conditional knockdown established genetically that NMT is essential for blood-stage survival, moving it from a biochemically active enzyme to a validated dependency.","evidence":"Tetracycline-repressible transactivator knockdown and viability assay in P. berghei","pmids":["23245327"],"confidence":"High","gaps":["Species is P. berghei, not P. falciparum","Which substrate(s) drive the lethal phenotype not identified","Stage-specific requirements not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2012,"claim":"The first Plasmodium NMT co-crystal structure with a screening hit defined the inhibitor binding mode and initiated structure-guided antimalarial design.","evidence":"High-throughput screening, high-resolution X-ray co-crystal structure, and structure-activity relationship analysis of P. vivax NMT","pmids":["22439843"],"confidence":"High","gaps":["Structure is from P. vivax NMT","Cellular efficacy not addressed by structure alone"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":2014,"claim":"A ternary NMT–CoA/myristoylated-peptide product structure provided direct mechanistic insight into the catalytic reaction and comparative binding across parasite NMTs.","evidence":"X-ray crystallography of ternary product complexes with P. falciparum and Leishmania NMTs plus enzyme inhibition assays","pmids":["25230674"],"confidence":"High","gaps":["Catalytic mechanism inferred from static structures","Substrate-selectivity determinants not fully mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Discovery that ACBD6 protects NMT from lauryl-CoA inhibition and enforces myristoyl-CoA preference identified a regulatory layer controlling acyl-CoA specificity under competing-substrate conditions.","evidence":"In vitro enzymatic activity and acyl-CoA competition assays with recombinant P. falciparum proteins","pmids":["30642881"],"confidence":"Medium","gaps":["Regulatory interaction shown in vitro; in vivo role in the parasite not established","Whether ACBD6 physically docks onto NMT not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Resistance mapping to a single substrate-pocket substitution confirmed that NMT itself is the antimalarial target of a specific inhibitor series and revealed a chemically distinct series that circumvents it.","evidence":"In vitro resistance selection, crystallography, enzyme activity, thermal stability, and surface plasmon resonance","pmids":["31080074"],"confidence":"High","gaps":["Fitness cost of the resistance mutation not characterized","Clinical relevance of resistance not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Chemical inhibition combined with substrate glycine-to-alanine mutagenesis dissected the pleiotropic, stage-specific consequences of NMT loss and showed substrate-specific myristoylation outcomes.","evidence":"NMT inhibitor treatment, N-terminal glycine-to-alanine substitution, chemical proteomics, microscopy, and egress/invasion assays in P. falciparum","pmids":["34695132"],"confidence":"High","gaps":["Mechanism by which unmyristoylated GAP45 fails at invasion despite normal localization is unresolved","Only a subset of the 16 affected substrates were functionally validated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"A 1.8 Å ternary structure with IMP-1088 showed the drug engages the parasite peptide-binding pocket much as it does the human enzyme, informing selectivity considerations.","evidence":"1.8 Å X-ray ternary complex of P. vivax NMT with myristoyl-CoA and IMP-1088","pmids":["39655507"],"confidence":"High","gaps":["Structure from P. vivax NMT","Selectivity margin over human NMT not quantified from structure alone"],"attribution":[{"species":"Plasmodium vivax","strain":""}]},{"year":null,"claim":"How NMT selects among its diverse substrates, how ACBD6 regulation operates in the living parasite, and how myristoylation controls each stage-specific function at the molecular level remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Full endogenous substrate set and selectivity code undefined","In vivo role of ACBD6–NMT regulation unconfirmed","Mechanistic basis of GAP45's myristoylation-dependent invasion function unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["NMT–AK2 heterodimer (in vitro) [#1]"],"partners":["ADENYLATE KINASE 2 (AK2) — SUBSTRATE AND HETERODIMER PARTNER [#1]","ACBD6 — ACYL-COA BINDING PROTEIN THAT REGULATES NMT ACYL-COA SPECIFICITY [#3]","GAP45 — DUALLY ACYLATED SUBSTRATE [#10, #4]"],"other_free_text":["Single-copy gene expressed as mRNA in asexual blood stages [#0]","Essential for blood-stage survival (P. berghei conditional knockdown) [#2]","Uses myristoyl-CoA as acyl donor; peptide-substrate and CoA pockets defined by ternary crystal structures [#7, #9]","Inhibitor sensitivity by chemical modification differs from human NMT [#0]","Single substrate-pocket amino acid substitution confers resistance to one inhibitor series [#5]","16 substrates showed reduced myristoylation upon inhibition; 6 reduced in abundance; 4 validated by glycine-to-alanine mutation [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16750579","id":"PMC_16750579","title":"Dual acylation of the 45 kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites.","date":"2006","source":"Molecular and biochemical 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microbe","url":"https://pubmed.ncbi.nlm.nih.gov/23245327","citation_count":76,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24641010","id":"PMC_24641010","title":"Design and synthesis of high affinity inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferases directed by ligand efficiency dependent lipophilicity (LELP).","date":"2014","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24641010","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22439843","id":"PMC_22439843","title":"Discovery of Plasmodium vivax N-myristoyltransferase inhibitors: screening, synthesis, and structural characterization of their binding 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sickness.","date":"2017","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/28270257","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25230674","id":"PMC_25230674","title":"Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites.","date":"2014","source":"Organic & biomolecular chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25230674","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31850752","id":"PMC_31850752","title":"Identification of Selective Inhibitors of Plasmodium N-Myristoyltransferase by High-Throughput Screening.","date":"2020","source":"Journal of medicinal 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into novel antimalarial drug design.","date":"2015","source":"Journal of molecular modeling","url":"https://pubmed.ncbi.nlm.nih.gov/25663521","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36002266","id":"PMC_36002266","title":"Identification of potential inhibitors for N-myristoyltransferase (NMT) protein of Plasmodium vivax.","date":"2022","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/36002266","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30342177","id":"PMC_30342177","title":"N-myristoyltransferases inhibitory activity of ellagitannins from Terminalia bentzoë (L.) L. f. subsp. bentzoë.","date":"2018","source":"Fitoterapia","url":"https://pubmed.ncbi.nlm.nih.gov/30342177","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39655507","id":"PMC_39655507","title":"Structure of Plasmodium vivaxN-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy.","date":"2025","source":"Acta crystallographica. Section F, Structural biology communications","url":"https://pubmed.ncbi.nlm.nih.gov/39655507","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22529627","id":"PMC_22529627","title":"Analyzing a Potential Drug Target N-Myristoyltransferase of Plasmodium falciparum Through In Silico Approaches.","date":"2012","source":"Journal of global infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/22529627","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39440556","id":"PMC_39440556","title":"Current trends to design antimalarial drugs targeting N-myristoyltransferase.","date":"2024","source":"Future microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/39440556","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38680035","id":"PMC_38680035","title":"Exploring Subsite Selectivity within Plasmodium vivax N-Myristoyltransferase Using Pyrazole-Derived Inhibitors.","date":"2024","source":"Journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/38680035","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38463971","id":"PMC_38463971","title":"Selective Bias Virtual Screening for Discovery of Promising Antimalarial Candidates targeting Plasmodium N-Myristoyltransferase.","date":"2024","source":"Research square","url":"https://pubmed.ncbi.nlm.nih.gov/38463971","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41011596","id":"PMC_41011596","title":"N-Myristoyltransferase Inhibition in Parasitic Pathogens: Insights from Computer-Aided Drug Design.","date":"2025","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/41011596","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40978577","id":"PMC_40978577","title":"Molecular docking analysis of N-myristoyl-transferase with small molecules from the ZINC database for screening potential anti-malarial drugs.","date":"2025","source":"Bioinformation","url":"https://pubmed.ncbi.nlm.nih.gov/40978577","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42368058","id":"PMC_42368058","title":"Design, Synthesis, and Antimalarial Evaluation of Novel Quinazolin-4(3H)‑one Derivatives with Molecular Modeling Insights into Target Selectivity.","date":"2026","source":"ACS omega","url":"https://pubmed.ncbi.nlm.nih.gov/42368058","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["NMT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":16664,"output_tokens":3221,"usd":0.049154,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":9080,"output_tokens":4131,"usd":0.074338,"stage2_stop_reason":"end_turn"},"total_usd":0.123492,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2000,\n      \"finding\": \"P. falciparum NMT (PF3D7_1412800) was cloned from P. falciparum, shown to be single-copy with mRNA expressed in asexual blood stages, and the recombinant protein expressed in E. coli was demonstrated to have myristoyltransferase enzymatic activity using a synthetic peptide substrate. The active-site residues important for substrate binding and catalysis in other species are conserved. Unlike human NMT, P. falciparum NMT activity was not inhibited by diethylpyrocarbonate or iodoacetamide, indicating a different pattern of inhibitor sensitivity by chemical modification.\",\n      \"method\": \"Gene cloning, cDNA/genomic sequence comparison, recombinant protein expression in E. coli, in vitro enzymatic activity assay with synthetic peptide substrate, chemical modification inhibition assays\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzymatic reconstitution with mutagenesis-level chemical probing; single lab but multiple orthogonal methods (cloning, expression, activity assay, chemical inhibition comparison)\",\n      \"pmids\": [\"10816442\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"P. falciparum NMT (PF3D7_1412800) was co-expressed with adenylate kinase 2 (AK2) in E. coli in the presence of myristate, and mass spectrometry confirmed that NMT catalyzes myristoylation of the intact malarial AK2 protein. Furthermore, AK2 and NMT were shown to interact strongly with each other, forming a heterodimeric protein complex in vitro.\",\n      \"method\": \"Heterologous co-expression in E. coli, protein purification, mass spectrometry for myristoylation confirmation, in vitro protein-protein interaction (heterodimer formation)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of myristoylation confirmed by mass spectrometry, plus direct protein-protein interaction shown; single lab, two orthogonal methods\",\n      \"pmids\": [\"18973776\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Tetracycline-induced conditional knockdown of N-myristoyltransferase (NMT) in P. berghei using a TetR-based transactivator system resulted in a dramatic reduction in parasite viability, establishing that NMT is essential for P. berghei blood-stage parasite survival.\",\n      \"method\": \"Conditional knockdown using tetracycline-repressible transactivator (TetR) system, parasite viability assay\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined viability phenotype in a genetic model; single lab but robust genetic system with clear phenotypic readout\",\n      \"pmids\": [\"23245327\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"ACBD6 (an acyl-CoA binding domain protein) supports and regulates the activity of P. falciparum NMT (PF3D7_1412800). ACBD6 protects NMT from inhibition by lauryl-CoA and promotes preferential use of myristoyl-CoA substrate, thereby enhancing N-myristoylation under substrate-limiting conditions where palmitoyl-CoA competes with myristoyl-CoA for NMT binding.\",\n      \"method\": \"In vitro enzymatic activity assays with recombinant proteins, acyl-CoA competition assays\",\n      \"journal\": \"Journal of lipid research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — in vitro functional reconstitution with defined substrate competition, single lab, single method set\",\n      \"pmids\": [\"30642881\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Treatment of P. falciparum with NMT inhibitor IMP-1002 during schizogony blocked parasite egress from erythrocytes, disrupted rhoptry protein localization, and impaired erythrocyte invasion. Sixteen NMT substrate proteins showed significantly reduced myristoylation upon NMTi treatment, of which six were substantially reduced in abundance. Replacement of the N-terminal glycine with alanine (preventing myristoylation) in four of these substrates substantially impaired parasite fitness. For GAP45 specifically, loss of myristoylation did not affect protein localization or glideosome assembly but was essential for erythrocyte invasion, demonstrating mechanistically distinct consequences of myristoylation for individual substrates. NMT inhibition thus disrupts parasite development at three stages: early schizogony (pseudoschizont formation), late schizogony (rhoptry formation/egress), and invasion.\",\n      \"method\": \"Chemical biology (NMT inhibitor treatment), genetic modification (N-terminal glycine-to-alanine substitution), parasite viability screen, chemical proteomics for myristoylation profiling, fluorescence microscopy for protein localization, parasite egress and invasion assays\",\n      \"journal\": \"PLoS biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (chemical inhibition, genetic mutation, chemical proteomics, functional assays) in a single rigorous study establishing pleiotropic mechanistic roles\",\n      \"pmids\": [\"34695132\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In vitro resistance to a specific NMT inhibitor series was mediated by a single amino acid substitution in the NMT substrate-binding pocket, validated by crystallography, enzyme activity assays, stability assays, and surface plasmon resonance. A second inhibitor series was identified that was unaffected by this substitution.\",\n      \"method\": \"In vitro resistance selection, crystallography, enzyme activity assays, thermal stability assays, surface plasmon resonance\",\n      \"journal\": \"Cell chemical biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus multiple orthogonal biochemical assays (SPR, enzyme kinetics, stability); single lab but multiple rigorous methods validating the resistance mechanism\",\n      \"pmids\": [\"31080074\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Crystal structure of P. vivax NMT in complex with a hit compound from high-throughput screening was obtained at high resolution, revealing the novel binding mode of the inhibitor in the NMT active site. Structure-activity relationships defined chemical groups relevant for activity and selectivity.\",\n      \"method\": \"High-throughput screening, X-ray crystallography (high-resolution co-crystal structure with inhibitor), structure-activity relationship analysis\",\n      \"journal\": \"Journal of medicinal chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure with functional (SAR) validation; single lab, two orthogonal methods\",\n      \"pmids\": [\"22439843\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"High-resolution crystal structures of peptidomimetic inhibitors in complex with P. falciparum NMT and Leishmania NMT were obtained, including the first crystal structure evidence for a ternary NMT–Coenzyme A/myristoylated peptide product complex, revealing comparative binding modes between Plasmodium and Leishmania NMTs.\",\n      \"method\": \"X-ray crystallography (ternary complex structure), enzyme inhibition assays\",\n      \"journal\": \"Organic & biomolecular chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure of ternary product complex providing direct mechanistic insight into the catalytic mechanism; single lab, structural and biochemical methods\",\n      \"pmids\": [\"25230674\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"NMT inhibition in P. falciparum results in incorrect localization of myristoylated substrate proteins, disrupting their membrane interactions and causing pleiotropic effects on parasite development, growth, and multiplication. NMT substrates include proteins involved in secretory transport and apicomplexan-specific processes including gliding motility.\",\n      \"method\": \"Review/perspective synthesizing chemical biology and inhibitor studies; substrate localization experiments cited from prior work\",\n      \"journal\": \"ACS infectious diseases\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — synthesis of experimental evidence from multiple studies; mechanistic claim about mislocalization supported by referenced experimental data\",\n      \"pmids\": [\"29363940\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"A 1.8 Å resolution ternary crystal structure of P. vivax NMT in complex with myristoyl-CoA and the inhibitor IMP-1088 was determined, showing that IMP-1088 binds PvNMT similarly to how it binds human NMT, occupying the peptide substrate-binding pocket.\",\n      \"method\": \"X-ray crystallography (1.8 Å ternary complex structure)\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — high-resolution crystal structure of ternary complex with functional inhibitor; single lab, rigorous structural determination\",\n      \"pmids\": [\"39655507\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"GAP45 in P. falciparum merozoites undergoes dual acylation: N-terminal myristoylation (catalyzed by NMT) and palmitoylation. This dual acylation is important for membrane association of GAP45.\",\n      \"method\": \"Metabolic labeling with [3H]-myristate and [3H]-palmitate, immunoprecipitation, mass spectrometry\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct biochemical demonstration of NMT-dependent myristoylation of a specific substrate; single lab, multiple labeling methods\",\n      \"pmids\": [\"16750579\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum NMT (PF3D7_1412800) is a cytosolic, single-copy, essential myristoyltransferase that co-translationally transfers myristate from myristoyl-CoA to the N-terminal glycine of diverse substrate proteins (including GAP45, AK2, and rhoptry proteins); its activity is regulated by the acyl-CoA binding protein ACBD6 which enforces myristoyl-CoA specificity, it forms a heterodimer with substrate AK2 in vitro, and its inhibition causes pleiotropic disruption of parasite development at three distinct stages—early schizogony, late schizogony/egress, and erythrocyte invasion—primarily through mislocalization or destabilization of myristoylated substrates essential for membrane targeting and parasite motility.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1412800 (NMT) is a single-copy, essential glycylpeptide N-tetradecanoyltransferase of Plasmodium that transfers myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins during asexual blood-stage development [#0, #2]. The recombinant enzyme is catalytically active on synthetic peptide substrates, its catalytic and substrate-binding residues are conserved, and it displays a chemical-inhibitor sensitivity distinct from the human enzyme [#0]. NMT myristoylates a defined set of parasite substrates including adenylate kinase 2 (AK2), with which it also forms a heterodimeric complex in vitro [#1], and the glideosome protein GAP45, which is dually acylated by N-terminal myristoylation and palmitoylation to support membrane association [#10]. Enzyme activity is regulated by the acyl-CoA binding protein ACBD6, which protects NMT from lauryl-CoA inhibition and enforces preferential use of myristoyl-CoA over competing palmitoyl-CoA [#3]. Pharmacological inhibition disrupts parasite development at three stages\\u2014early schizogony, late schizogony/egress, and erythrocyte invasion\\u2014by reducing myristoylation and destabilizing or mislocalizing substrate proteins, with substrate-specific consequences: for GAP45, loss of myristoylation spares localization and glideosome assembly yet is still required for invasion [#4, #8]. High-resolution ternary crystal structures of Plasmodium NMTs capture the enzyme with myristoyl-CoA and peptidomimetic or drug-like inhibitors bound in the peptide-substrate pocket, and a single substitution in that pocket confers resistance to one inhibitor series, validating the active site as an antimalarial target [#5, #6, #7, #9].\",\n  \"teleology\": [\n    {\n      \"year\": 2000,\n      \"claim\": \"Establishing that Plasmodium encodes a genuine myristoyltransferase answered whether the parasite possesses this enzymatic machinery and whether its catalytic properties differ from the human host enzyme.\",\n      \"evidence\": \"Cloning, sequence comparison, recombinant expression in E. coli, in vitro activity assay on a synthetic peptide, and chemical-modification inhibition comparisons\",\n      \"pmids\": [\"10816442\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Endogenous substrate repertoire not defined\", \"Subcellular localization in the parasite not established\", \"Essentiality not yet tested genetically\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Identifying GAP45 as a dually acylated NMT substrate connected the enzyme to a specific membrane-targeting event in merozoites.\",\n      \"evidence\": \"Metabolic labeling with [3H]-myristate and [3H]-palmitate, immunoprecipitation, and mass spectrometry in P. falciparum\",\n      \"pmids\": [\"16750579\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional requirement of GAP45 myristoylation for invasion not yet dissected here\", \"Interplay of myristoylation and palmitoylation timing unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Demonstrating myristoylation of intact AK2 and a stable NMT\\u2013AK2 heterodimer showed NMT acts on a full-length parasite protein and can form a defined complex with a substrate.\",\n      \"evidence\": \"Co-expression in E. coli with myristate, purification, mass spectrometry, and in vitro protein-protein interaction\",\n      \"pmids\": [\"18973776\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological relevance of the heterodimer in vivo unknown\", \"Whether heterodimerization reflects a general substrate-engagement mode or is AK2-specific is unclear\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Conditional knockdown established genetically that NMT is essential for blood-stage survival, moving it from a biochemically active enzyme to a validated dependency.\",\n      \"evidence\": \"Tetracycline-repressible transactivator knockdown and viability assay in P. berghei\",\n      \"pmids\": [\"23245327\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Species is P. berghei, not P. falciparum\", \"Which substrate(s) drive the lethal phenotype not identified\", \"Stage-specific requirements not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The first Plasmodium NMT co-crystal structure with a screening hit defined the inhibitor binding mode and initiated structure-guided antimalarial design.\",\n      \"evidence\": \"High-throughput screening, high-resolution X-ray co-crystal structure, and structure-activity relationship analysis of P. vivax NMT\",\n      \"pmids\": [\"22439843\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure is from P. vivax NMT\", \"Cellular efficacy not addressed by structure alone\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"A ternary NMT\\u2013CoA/myristoylated-peptide product structure provided direct mechanistic insight into the catalytic reaction and comparative binding across parasite NMTs.\",\n      \"evidence\": \"X-ray crystallography of ternary product complexes with P. falciparum and Leishmania NMTs plus enzyme inhibition assays\",\n      \"pmids\": [\"25230674\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Catalytic mechanism inferred from static structures\", \"Substrate-selectivity determinants not fully mapped\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Discovery that ACBD6 protects NMT from lauryl-CoA inhibition and enforces myristoyl-CoA preference identified a regulatory layer controlling acyl-CoA specificity under competing-substrate conditions.\",\n      \"evidence\": \"In vitro enzymatic activity and acyl-CoA competition assays with recombinant P. falciparum proteins\",\n      \"pmids\": [\"30642881\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Regulatory interaction shown in vitro; in vivo role in the parasite not established\", \"Whether ACBD6 physically docks onto NMT not resolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Resistance mapping to a single substrate-pocket substitution confirmed that NMT itself is the antimalarial target of a specific inhibitor series and revealed a chemically distinct series that circumvents it.\",\n      \"evidence\": \"In vitro resistance selection, crystallography, enzyme activity, thermal stability, and surface plasmon resonance\",\n      \"pmids\": [\"31080074\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Fitness cost of the resistance mutation not characterized\", \"Clinical relevance of resistance not established\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Chemical inhibition combined with substrate glycine-to-alanine mutagenesis dissected the pleiotropic, stage-specific consequences of NMT loss and showed substrate-specific myristoylation outcomes.\",\n      \"evidence\": \"NMT inhibitor treatment, N-terminal glycine-to-alanine substitution, chemical proteomics, microscopy, and egress/invasion assays in P. falciparum\",\n      \"pmids\": [\"34695132\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which unmyristoylated GAP45 fails at invasion despite normal localization is unresolved\", \"Only a subset of the 16 affected substrates were functionally validated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A 1.8 \\u00c5 ternary structure with IMP-1088 showed the drug engages the parasite peptide-binding pocket much as it does the human enzyme, informing selectivity considerations.\",\n      \"evidence\": \"1.8 \\u00c5 X-ray ternary complex of P. vivax NMT with myristoyl-CoA and IMP-1088\",\n      \"pmids\": [\"39655507\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structure from P. vivax NMT\", \"Selectivity margin over human NMT not quantified from structure alone\"],\n      \"attribution\": [{\"species\": \"Plasmodium vivax\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NMT selects among its diverse substrates, how ACBD6 regulation operates in the living parasite, and how myristoylation controls each stage-specific function at the molecular level remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Full endogenous substrate set and selectivity code undefined\", \"In vivo role of ACBD6\\u2013NMT regulation unconfirmed\", \"Mechanistic basis of GAP45's myristoylation-dependent invasion function unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004379\", \"supporting_discovery_ids\": [0, 1, 3, 4, 7, 10]},\n      {\"term_id\": \"GO:0072586\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006499\", \"supporting_discovery_ids\": [0, 1, 10, 4]},\n      {\"term_id\": \"GO:0006935\", \"supporting_discovery_ids\": [4, 8]},\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"NMT\\u2013AK2 heterodimer (in vitro) [#1]\"\n    ],\n    \"partners\": [\n      \"Adenylate kinase 2 (AK2) \\u2014 substrate and heterodimer partner [#1]\",\n      \"ACBD6 \\u2014 acyl-CoA binding protein that regulates NMT acyl-CoA specificity [#3]\",\n      \"GAP45 \\u2014 dually acylated substrate [#10, #4]\"\n    ],\n    \"other_free_text\": [\n      \"Single-copy gene expressed as mRNA in asexual blood stages [#0]\",\n      \"Essential for blood-stage survival (P. berghei conditional knockdown) [#2]\",\n      \"Uses myristoyl-CoA as acyl donor; peptide-substrate and CoA pockets defined by ternary crystal structures [#7, #9]\",\n      \"Inhibitor sensitivity by chemical modification differs from human NMT [#0]\",\n      \"Single substrate-pocket amino acid substitution confers resistance to one inhibitor series [#5]\",\n      \"16 substrates showed reduced myristoylation upon inhibition; 6 reduced in abundance; 4 validated by glycine-to-alanine mutation [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1412800","name":null,"product":"glycylpeptide N-tetradecanoyltransferase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1029800","name":null,"product":"glycylpeptide N-tetradecanoyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1345500","name":null,"product":"glycylpeptide N-tetradecanoyltransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"NMT","evaluation":null}