{"gene":"TG_209160","gene_symbol":"NMT","run_date":"2026-09-08T11:06:20","timeline":{"discoveries":[{"year":2019,"finding":"Toxoplasma gondii encodes a putative N-myristoyltransferase (TgNMT) that is homologous to other parasitic NMTs, demonstrates N-myristoyltransferase activity in vitro, is expressed in both intra- and extracellular parasites, interacts with predicted TgNMT substrates, and NMT activity is important for the lytic cycle of T. gondii.","method":"In vitro enzymatic activity assay, co-immunoprecipitation/interaction with substrates, expression profiling in intra- and extracellular parasites, lytic cycle assay with NMT inhibition","journal":"Experimental parasitology","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — in vitro enzymatic activity demonstrated and substrate interactions shown, but single lab and limited orthogonal validation of mechanistic pathway placement","pmids":["31150653"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgNMT is inhibited by a small-molecule NMT inhibitor developed against Plasmodium spp., demonstrating functional conservation of the enzyme across apicomplexan parasites.","method":"Chemoproteomic profiling with small-molecule NMT inhibitor treatment in T. gondii","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — chemoproteomic approach with functional inhibitor readout, single lab but multiple orthogonal methods (chemical biology + proteomics)","pmids":["32618271"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgNMT myristoylates the microneme protein MIC7, which enters the secretory pathway unconventionally with its myristoylated N-terminus facing the lumen of the micronemes; this myristoylation on MIC7 is required for the initial steps of host cell invasion, likely during interaction with and penetration of the host cell.","method":"Chemoproteomic myristoylome profiling, identification of MIC7 as a myristoylated substrate, functional loss-of-function/myristoylation-site mutant assays for host cell penetration","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — chemoproteomic substrate identification combined with functional invasion assays and unconventional topology characterization, multiple orthogonal methods in single rigorous study","pmids":["32618271"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgNMT is an active N-myristoyltransferase that co-translationally myristoylates a defined set of T. gondii proteins (including the microneme protein MIC7), is essential for the parasite lytic cycle, and can be inhibited by small-molecule NMT inhibitors developed against Plasmodium, with myristoylation of secreted proteins like MIC7 playing direct roles in host cell invasion."},"narrative":{"mechanistic_narrative":"TgNMT is the Toxoplasma gondii N-myristoyltransferase, an enzyme with demonstrated in vitro myristoyltransferase activity that is expressed in both intra- and extracellular parasites, interacts with predicted substrates, and whose activity is required for the parasite lytic cycle [PMID:31150653]. It can be blocked by a small-molecule NMT inhibitor originally developed against Plasmodium, establishing functional conservation of the enzyme across apicomplexan parasites [PMID:32618271]. Among its substrates is the microneme protein MIC7, which enters the secretory pathway unconventionally with its myristoylated N-terminus facing the microneme lumen; this modification is required for the initial steps of host cell invasion [PMID:32618271]. Beyond this substrate set and its role in invasion, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Establishing that the T. gondii genome-encoded NMT is a bona fide active enzyme relevant to parasite biology answered whether myristoylation is enzymatically operative and functionally important in this parasite.","evidence":"In vitro enzymatic activity assay, co-immunoprecipitation with predicted substrates, expression profiling, and lytic cycle assay under NMT inhibition in T. gondii","pmids":["31150653"],"confidence":"Medium","gaps":["Specific endogenous substrates were not yet defined","Mechanistic pathway placement validated in a single lab with limited orthogonal support"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Showing that a Plasmodium-directed NMT inhibitor also blocks TgNMT answered whether the enzyme is chemically tractable and conserved across apicomplexans, supporting cross-parasite drug targeting.","evidence":"Chemoproteomic profiling with small-molecule NMT inhibitor treatment in T. gondii","pmids":["32618271"],"confidence":"Medium","gaps":["Inhibitor selectivity and off-target effects within the parasite not fully resolved","Structural basis of inhibitor binding not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Identifying MIC7 as a myristoylated substrate and linking its modification to invasion answered how NMT activity mechanistically contributes to the lytic cycle, connecting a single modification to a defined biological step.","evidence":"Chemoproteomic myristoylome profiling, MIC7 substrate identification, unconventional topology characterization, and myristoylation-site mutant host-penetration assays","pmids":["32618271"],"confidence":"High","gaps":["The molecular mechanism by which luminal myristoylation of MIC7 aids penetration is unresolved","The full complement of TgNMT substrates beyond MIC7 is not defined","How MIC7 achieves unconventional secretory-pathway entry with a luminal myristoyl group is unexplained"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether other myristoylated TgNMT substrates contribute to distinct steps of the lytic cycle, and how myristoylation is mechanistically coupled to protein trafficking and invasion, remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of TgNMT","Substrate repertoire beyond MIC7 uncharacterized","Mechanism linking myristoylation to invasion function unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MIC7 (MYRISTOYLATED SUBSTRATE)"],"other_free_text":["TgNMT activity is required for the T. gondii lytic cycle [#0]","Inhibited by a small-molecule NMT inhibitor developed against Plasmodium, indicating cross-apicomplexan functional conservation [#1]","Myristoylation of MIC7 is required for the initial steps of host cell invasion; MIC7 enters the secretory pathway unconventionally with its myristoylated N-terminus facing the microneme lumen [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"32618271","id":"PMC_32618271","title":"Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/32618271","citation_count":25,"is_preprint":false},{"pmid":"31150653","id":"PMC_31150653","title":"Exploring protein myristoylation in Toxoplasma gondii.","date":"2019","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/31150653","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3317,"output_tokens":907,"usd":0.011778,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5715,"output_tokens":1821,"usd":0.03705,"stage2_stop_reason":"end_turn"},"total_usd":0.048828,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"Toxoplasma gondii encodes a putative N-myristoyltransferase (TgNMT) that is homologous to other parasitic NMTs, demonstrates N-myristoyltransferase activity in vitro, is expressed in both intra- and extracellular parasites, interacts with predicted TgNMT substrates, and NMT activity is important for the lytic cycle of T. gondii.\",\n      \"method\": \"In vitro enzymatic activity assay, co-immunoprecipitation/interaction with substrates, expression profiling in intra- and extracellular parasites, lytic cycle assay with NMT inhibition\",\n      \"journal\": \"Experimental parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — in vitro enzymatic activity demonstrated and substrate interactions shown, but single lab and limited orthogonal validation of mechanistic pathway placement\",\n      \"pmids\": [\"31150653\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgNMT is inhibited by a small-molecule NMT inhibitor developed against Plasmodium spp., demonstrating functional conservation of the enzyme across apicomplexan parasites.\",\n      \"method\": \"Chemoproteomic profiling with small-molecule NMT inhibitor treatment in T. gondii\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — chemoproteomic approach with functional inhibitor readout, single lab but multiple orthogonal methods (chemical biology + proteomics)\",\n      \"pmids\": [\"32618271\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgNMT myristoylates the microneme protein MIC7, which enters the secretory pathway unconventionally with its myristoylated N-terminus facing the lumen of the micronemes; this myristoylation on MIC7 is required for the initial steps of host cell invasion, likely during interaction with and penetration of the host cell.\",\n      \"method\": \"Chemoproteomic myristoylome profiling, identification of MIC7 as a myristoylated substrate, functional loss-of-function/myristoylation-site mutant assays for host cell penetration\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — chemoproteomic substrate identification combined with functional invasion assays and unconventional topology characterization, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"32618271\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgNMT is an active N-myristoyltransferase that co-translationally myristoylates a defined set of T. gondii proteins (including the microneme protein MIC7), is essential for the parasite lytic cycle, and can be inhibited by small-molecule NMT inhibitors developed against Plasmodium, with myristoylation of secreted proteins like MIC7 playing direct roles in host cell invasion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgNMT is the Toxoplasma gondii N-myristoyltransferase, an enzyme with demonstrated in vitro myristoyltransferase activity that is expressed in both intra- and extracellular parasites, interacts with predicted substrates, and whose activity is required for the parasite lytic cycle [#0]. It can be blocked by a small-molecule NMT inhibitor originally developed against Plasmodium, establishing functional conservation of the enzyme across apicomplexan parasites [#1]. Among its substrates is the microneme protein MIC7, which enters the secretory pathway unconventionally with its myristoylated N-terminus facing the microneme lumen; this modification is required for the initial steps of host cell invasion [#2]. Beyond this substrate set and its role in invasion, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing that the T. gondii genome-encoded NMT is a bona fide active enzyme relevant to parasite biology answered whether myristoylation is enzymatically operative and functionally important in this parasite.\",\n      \"evidence\": \"In vitro enzymatic activity assay, co-immunoprecipitation with predicted substrates, expression profiling, and lytic cycle assay under NMT inhibition in T. gondii\",\n      \"pmids\": [\"31150653\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific endogenous substrates were not yet defined\",\n        \"Mechanistic pathway placement validated in a single lab with limited orthogonal support\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Showing that a Plasmodium-directed NMT inhibitor also blocks TgNMT answered whether the enzyme is chemically tractable and conserved across apicomplexans, supporting cross-parasite drug targeting.\",\n      \"evidence\": \"Chemoproteomic profiling with small-molecule NMT inhibitor treatment in T. gondii\",\n      \"pmids\": [\"32618271\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Inhibitor selectivity and off-target effects within the parasite not fully resolved\",\n        \"Structural basis of inhibitor binding not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identifying MIC7 as a myristoylated substrate and linking its modification to invasion answered how NMT activity mechanistically contributes to the lytic cycle, connecting a single modification to a defined biological step.\",\n      \"evidence\": \"Chemoproteomic myristoylome profiling, MIC7 substrate identification, unconventional topology characterization, and myristoylation-site mutant host-penetration assays\",\n      \"pmids\": [\"32618271\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The molecular mechanism by which luminal myristoylation of MIC7 aids penetration is unresolved\",\n        \"The full complement of TgNMT substrates beyond MIC7 is not defined\",\n        \"How MIC7 achieves unconventional secretory-pathway entry with a luminal myristoyl group is unexplained\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether other myristoylated TgNMT substrates contribute to distinct steps of the lytic cycle, and how myristoylation is mechanistically coupled to protein trafficking and invasion, remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of TgNMT\",\n        \"Substrate repertoire beyond MIC7 uncharacterized\",\n        \"Mechanism linking myristoylation to invasion function unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004379\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006499\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MIC7 (myristoylated substrate)\"],\n    \"other_free_text\": [\n      \"TgNMT activity is required for the T. gondii lytic cycle [#0]\",\n      \"Inhibited by a small-molecule NMT inhibitor developed against Plasmodium, indicating cross-apicomplexan functional conservation [#1]\",\n      \"Myristoylation of MIC7 is required for the initial steps of host cell invasion; MIC7 enters the secretory pathway unconventionally with its myristoylated N-terminus facing the microneme lumen [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_209160","name":"NMT","product":"myristoyl CoA:protein N-myristoyltransferase","uniprot_acc":"A0A125YVL2","chromosome":"TGME49_chrIb","start_pos":1079617},{"strain":"GT1","gene_id":"TGGT1_209160","name":null,"product":"myristoyl CoA:protein N-myristoyltransferase","uniprot_acc":null,"chromosome":"TGGT1_chrIb","start_pos":1097244},{"strain":"RH88","gene_id":"TGRH88_021930","name":null,"product":"myristoyl CoA:protein N-myristoyltransferase","uniprot_acc":null,"chromosome":"CM023082","start_pos":922126},{"strain":"VEG","gene_id":"TGVEG_209160","name":null,"product":"myristoyl CoA:protein N-myristoyltransferase","uniprot_acc":"A0A125YVL3","chromosome":"TGVEG_chrIb","start_pos":1079939}]}