{"gene":"PF3D7_0416100","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2015,"finding":"PF3D7_0416100 (GatA subunit of the apicoplast glutamyl-tRNA(Gln) amidotransferase) was localized to the apicoplast in P. falciparum blood-stage parasites by direct subcellular localization experiments, and recombinant GatAB heterodimer (comprising GatA and GatB subunits) was shown to convert Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro, demonstrating its enzymatic amidotransferase activity.","method":"Subcellular localization (fluorescence microscopy), in vitro enzymatic reconstitution with recombinant protein","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct in vitro enzymatic reconstitution of the GatAB heterodimer plus subcellular localization, single lab but two orthogonal methods","pmids":["26318454"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The GatA subunit (PF3D7_0416100) is essential for P. berghei blood-stage parasite survival: attempts to delete the gene encoding GatA in blood-stage P. berghei parasites in vivo failed, demonstrating that the apicoplast GatAB-catalyzed Gln-tRNA(Gln) biosynthesis pathway is indispensable.","method":"Gene knockout attempt in P. berghei blood-stage parasites (negative result indicating essentiality)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean in vivo knockout attempt with defined lethal phenotype, single lab, single method","pmids":["26318454"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"finding":"Plasmodium GatA (PF3D7_0416100) and GatB form a unique heterodimeric amidotransferase (GatAB) that is distinct from canonical bacterial GatCAB trimers and archaeal GatDE heterodimers; phylogenetic analysis indicates both GatA and GatB subunits emerged prior to the bacterial-archaeal phylogenetic divide.","method":"Phylogenetic analysis combined with biochemical reconstitution","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — reconstitution supports the functional uniqueness of the heterodimer; phylogenetic analysis is computational but supported by biochemical data in the same study, single lab","pmids":["26318454"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0416100 (GatA) is the A subunit of a unique heterodimeric glutamyl-tRNA(Gln) amidotransferase (GatAB) localized to the P. falciparum apicoplast, where it partners with GatB to convert mischarged Glu-tRNA(Gln) to Gln-tRNA(Gln) via an indirect aminoacylation pathway; this activity is essential for blood-stage parasite survival, as demonstrated by failed gene deletion in P. berghei and in vitro enzymatic reconstitution of the heterodimer."},"narrative":{"mechanistic_narrative":"PF3D7_0416100 (GatA) is the A subunit of a glutamyl-tRNA(Gln) amidotransferase that operates within the apicoplast of P. falciparum to support indirect aminoacylation of tRNA(Gln) [PMID:26318454]. Together with GatB it forms a heterodimeric GatAB enzyme; recombinant reconstitution of this heterodimer converts mischarged Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro, and immunolocalization places GatA in the apicoplast of blood-stage parasites [PMID:26318454]. This GatAB heterodimer is architecturally distinct from canonical bacterial GatCAB trimers and archaeal GatDE heterodimers, with both subunits arising before the bacterial-archaeal divide [PMID:26318454]. The pathway is essential for parasite blood-stage survival, as deletion of the GatA gene in P. berghei failed to yield viable parasites [PMID:26318454]. Beyond its role in the GatAB heterodimer, its catalytic mechanism at the residue level and structural organization have not been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Whether Plasmodium possesses an apicoplast-localized amidotransferase capable of correcting mischarged Glu-tRNA(Gln) was unknown; localization and in vitro reconstitution established GatA as an apicoplast enzyme subunit with amidotransferase activity.","evidence":"Fluorescence subcellular localization plus in vitro enzymatic reconstitution of the recombinant GatAB heterodimer in P. falciparum","pmids":["26318454"],"confidence":"High","gaps":["Catalytic contribution of the GatA subunit versus GatB not dissected","No structural model of the heterodimer","Residue-level mechanism of transamidation not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Whether GatAB-mediated Gln-tRNA(Gln) biosynthesis is required for parasite viability was untested; a failed knockout established the pathway as essential for blood-stage survival.","evidence":"In vivo gene knockout attempt in P. berghei blood-stage parasites yielding a lethal phenotype (negative deletion result)","pmids":["26318454"],"confidence":"Medium","gaps":["Essentiality shown by failed deletion, not conditional knockdown","Demonstrated in P. berghei rather than P. falciparum","Stage specificity beyond blood stage not addressed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"claim":"The evolutionary and structural class of the Plasmodium amidotransferase was unknown; combined phylogenetic and biochemical analysis established GatAB as a unique heterodimer distinct from bacterial GatCAB and archaeal GatDE.","evidence":"Phylogenetic analysis combined with biochemical reconstitution in P. falciparum","pmids":["26318454"],"confidence":"Medium","gaps":["Phylogenetic inference is computational","Functional consequence of the unique heterodimeric architecture not tested","Absence of a GatC-equivalent subunit not experimentally probed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The structural basis of GatA catalysis, its specific residue-level contribution to transamidation, and whether it could serve as a selective antimalarial target remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal or cryo-EM structure of the GatAB heterodimer","GatA active-site residues not mapped","No inhibitor or druggability data"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["GatAB glutamyl-tRNA(Gln) amidotransferase heterodimer (GatA + GatB)"],"partners":["GATB"],"other_free_text":["Essential for P. berghei blood-stage survival by failed gene deletion [#1]","GatAB heterodimer is architecturally distinct from bacterial GatCAB trimers and archaeal GatDE heterodimers [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"26318454","id":"PMC_26318454","title":"Plasmodium Apicoplast Gln-tRNAGln Biosynthesis Utilizes a Unique GatAB Amidotransferase Essential for Erythrocytic Stage Parasites.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/26318454","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39946429","id":"","title":"Spatial distribution of Plasmodium vivax Duffy Binding Protein copy number variation and Duffy genotype, and their association with parasitemia in Ethiopia.","date":"2025","source":"PLoS neglected tropical 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Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35735506","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38173794","id":"","title":"Novel stem cell technologies are powerful tools to understand the impact of human factors on Plasmodium falciparum malaria.","date":"2023","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38173794","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36361552","id":"","title":"Erythropoiesis and Malaria, a Multifaceted Interplay.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36361552","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38056460","id":"","title":"Unveiling P. vivax invasion pathways in Duffy-negative individuals.","date":"2023","source":"Cell host & microbe","url":"https://pubmed.ncbi.nlm.nih.gov/38056460","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37098534","id":"","title":"Differential transmissibility to Anopheles arabiensis of Plasmodium vivax gametocytes in patients with diverse Duffy blood group genotypes.","date":"2023","source":"Malaria 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disease","url":"https://pubmed.ncbi.nlm.nih.gov/37888606","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39452740","id":"","title":"Transcriptomic and Proteomic Insights into Host Immune Responses in Pediatric Severe Malarial Anemia: Dysregulation in HSP60-70-TLR2/4 Signaling and Altered Glutamine Metabolism.","date":"2024","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/39452740","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32556188","id":"","title":"Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.","date":"2022","source":"The Journal of infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32556188","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35946633","id":"","title":"Serological and Molecular Study of the Duffy Blood Group among Malarial Endemic Region Residents in Brazil.","date":"2022","source":"Revista da Sociedade Brasileira de Medicina Tropical","url":"https://pubmed.ncbi.nlm.nih.gov/35946633","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GATA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18798,"output_tokens":995,"usd":0.035659,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5738,"output_tokens":1801,"usd":0.036858,"stage2_stop_reason":"end_turn"},"total_usd":0.072517,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2015,\n      \"finding\": \"PF3D7_0416100 (GatA subunit of the apicoplast glutamyl-tRNA(Gln) amidotransferase) was localized to the apicoplast in P. falciparum blood-stage parasites by direct subcellular localization experiments, and recombinant GatAB heterodimer (comprising GatA and GatB subunits) was shown to convert Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro, demonstrating its enzymatic amidotransferase activity.\",\n      \"method\": \"Subcellular localization (fluorescence microscopy), in vitro enzymatic reconstitution with recombinant protein\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct in vitro enzymatic reconstitution of the GatAB heterodimer plus subcellular localization, single lab but two orthogonal methods\",\n      \"pmids\": [\"26318454\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The GatA subunit (PF3D7_0416100) is essential for P. berghei blood-stage parasite survival: attempts to delete the gene encoding GatA in blood-stage P. berghei parasites in vivo failed, demonstrating that the apicoplast GatAB-catalyzed Gln-tRNA(Gln) biosynthesis pathway is indispensable.\",\n      \"method\": \"Gene knockout attempt in P. berghei blood-stage parasites (negative result indicating essentiality)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean in vivo knockout attempt with defined lethal phenotype, single lab, single method\",\n      \"pmids\": [\"26318454\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Plasmodium GatA (PF3D7_0416100) and GatB form a unique heterodimeric amidotransferase (GatAB) that is distinct from canonical bacterial GatCAB trimers and archaeal GatDE heterodimers; phylogenetic analysis indicates both GatA and GatB subunits emerged prior to the bacterial-archaeal phylogenetic divide.\",\n      \"method\": \"Phylogenetic analysis combined with biochemical reconstitution\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — reconstitution supports the functional uniqueness of the heterodimer; phylogenetic analysis is computational but supported by biochemical data in the same study, single lab\",\n      \"pmids\": [\"26318454\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0416100 (GatA) is the A subunit of a unique heterodimeric glutamyl-tRNA(Gln) amidotransferase (GatAB) localized to the P. falciparum apicoplast, where it partners with GatB to convert mischarged Glu-tRNA(Gln) to Gln-tRNA(Gln) via an indirect aminoacylation pathway; this activity is essential for blood-stage parasite survival, as demonstrated by failed gene deletion in P. berghei and in vitro enzymatic reconstitution of the heterodimer.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0416100 (GatA) is the A subunit of a glutamyl-tRNA(Gln) amidotransferase that operates within the apicoplast of P. falciparum to support indirect aminoacylation of tRNA(Gln) [#0]. Together with GatB it forms a heterodimeric GatAB enzyme; recombinant reconstitution of this heterodimer converts mischarged Glu-tRNA(Gln) to Gln-tRNA(Gln) in vitro, and immunolocalization places GatA in the apicoplast of blood-stage parasites [#0]. This GatAB heterodimer is architecturally distinct from canonical bacterial GatCAB trimers and archaeal GatDE heterodimers, with both subunits arising before the bacterial-archaeal divide [#2]. The pathway is essential for parasite blood-stage survival, as deletion of the GatA gene in P. berghei failed to yield viable parasites [#1]. Beyond its role in the GatAB heterodimer, its catalytic mechanism at the residue level and structural organization have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether Plasmodium possesses an apicoplast-localized amidotransferase capable of correcting mischarged Glu-tRNA(Gln) was unknown; localization and in vitro reconstitution established GatA as an apicoplast enzyme subunit with amidotransferase activity.\",\n      \"evidence\": \"Fluorescence subcellular localization plus in vitro enzymatic reconstitution of the recombinant GatAB heterodimer in P. falciparum\",\n      \"pmids\": [\"26318454\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Catalytic contribution of the GatA subunit versus GatB not dissected\", \"No structural model of the heterodimer\", \"Residue-level mechanism of transamidation not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether GatAB-mediated Gln-tRNA(Gln) biosynthesis is required for parasite viability was untested; a failed knockout established the pathway as essential for blood-stage survival.\",\n      \"evidence\": \"In vivo gene knockout attempt in P. berghei blood-stage parasites yielding a lethal phenotype (negative deletion result)\",\n      \"pmids\": [\"26318454\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Essentiality shown by failed deletion, not conditional knockdown\", \"Demonstrated in P. berghei rather than P. falciparum\", \"Stage specificity beyond blood stage not addressed\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"The evolutionary and structural class of the Plasmodium amidotransferase was unknown; combined phylogenetic and biochemical analysis established GatAB as a unique heterodimer distinct from bacterial GatCAB and archaeal GatDE.\",\n      \"evidence\": \"Phylogenetic analysis combined with biochemical reconstitution in P. falciparum\",\n      \"pmids\": [\"26318454\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Phylogenetic inference is computational\", \"Functional consequence of the unique heterodimeric architecture not tested\", \"Absence of a GatC-equivalent subunit not experimentally probed\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural basis of GatA catalysis, its specific residue-level contribution to transamidation, and whether it could serve as a selective antimalarial target remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystal or cryo-EM structure of the GatAB heterodimer\", \"GatA active-site residues not mapped\", \"No inhibitor or druggability data\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0050567\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016810\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006424\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0006412\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"GatAB glutamyl-tRNA(Gln) amidotransferase heterodimer (GatA + GatB)\"],\n    \"partners\": [\"GatB\"],\n    \"other_free_text\": [\n      \"Essential for P. berghei blood-stage survival by failed gene deletion [#1]\",\n      \"GatAB heterodimer is architecturally distinct from bacterial GatCAB trimers and archaeal GatDE heterodimers [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0416100","name":null,"product":"glutamyl-tRNA(Gln) amidotransferase subunit A","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0718100","name":null,"product":"glutamyl-tRNA(Gln) amidotransferase subunit A","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0508500","name":null,"product":"glutamyl-tRNA(Gln) amidotransferase subunit A, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GATA","evaluation":null}