{"gene":"PF3D7_0204500","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2001,"finding":"P. falciparum AspAT (PF3D7_0204500) was cloned, expressed as recombinant protein, and shown to catalyze aspartate-ketoglutarate, tyrosine-ketoglutarate, and amino acid-ketomethiobutyrate aminotransfer reactions in vitro. The P. falciparum enzyme is unique in lacking the invariant residue G197 conserved across the Ia subfamily of aminotransferases, and it catalyzes ketomethiobutyrate transamination significantly more slowly than aspartate-ketoglutarate aminotransfer. Canaline was identified as an uncompetitive inhibitor with a Ki of 27 µM. The enzyme was shown to function in the final step of methionine regeneration from methylthioadenosine.","method":"Recombinant protein expression, in vitro enzymatic assays with multiple substrates, kinetic analysis, inhibitor characterization","journal":"Journal of bacteriology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — recombinant enzyme reconstitution with multiple in vitro kinetic assays and inhibitor characterization in a single rigorous study","pmids":["11443076"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"PfAspAT (PF3D7_0204500) was crystallized and its X-ray structure solved as a homodimer at 2.8 Å resolution. The overall fold is similar to other AspATs but shows significant divergence in the conformation of the N-terminal residues. Deletion of these divergent N-terminal residues results in loss of catalytic activity for the recombinant protein. Addition of a peptide containing the 13 divergent N-terminal residues inhibits PfAspAT activity both in vitro and in parasite lysates, while leaving human cytosolic AspAT unaffected. The enzyme was localized to the parasite cytosol by direct experiment.","method":"X-ray crystallography (2.8 Å), N-terminal deletion mutagenesis, in vitro enzymatic activity assay, parasite lysate activity assay, subcellular localization","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure, active-site mutagenesis, and in vitro + in situ functional validation in one study","pmids":["21087616"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"In intraerythrocytic P. falciparum, fumarate (a side product of the purine salvage pathway) is converted to aspartate via malate and oxaloacetate. Isotope tracing with [2,3-14C]fumarate and [2,3-13C]fumarate showed incorporation into nucleic acid, protein, malate, and aspartate fractions. Treatment with atovaquone (an electron transport chain inhibitor) blocked the conversion of fumarate to aspartate, establishing that PfAspAT (aspartate aminotransferase) operates downstream of malate quinone oxidoreductase in an electron transport chain-dependent biosynthetic pathway supplying aspartate for nucleic acid and protein synthesis.","method":"Radioisotope labeling ([2,3-14C]fumarate), 13C NMR metabolite tracing, atovaquone inhibition experiment in free parasites","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — two orthogonal isotope-tracing methods plus pharmacological pathway dissection in intact parasites, single lab","pmids":["21209090"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"PfAspAT (PF3D7_0204500) was successfully expressed, purified to homogeneity, and crystallized, yielding a 2.8 Å diffraction dataset used for structure determination by molecular replacement, confirming the protein is amenable to structural analysis.","method":"Recombinant protein expression, purification, crystallization, X-ray diffraction data collection","journal":"Acta crystallographica. Section F, Structural biology and crystallization communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — structural crystallography report from single lab; preliminary findings superseded by the full structure paper (PMID 21087616)","pmids":["20383010"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0204500 (AspAT) is a cytosolic homodimeric pyridoxal-5'-phosphate-dependent aspartate aminotransferase in P. falciparum whose 2.8 Å crystal structure reveals a divergent N-terminal region essential for catalytic activity; it converts aspartate and α-ketoglutarate to oxaloacetate and glutamate, operates downstream of the mitochondrial electron transport chain to channel fumarate-derived carbons into aspartate for nucleic acid and protein biosynthesis, and also catalyzes the final transamination step in methionine regeneration from methylthioadenosine, with its unique N-terminal residues offering a basis for parasite-selective inhibition."},"narrative":{"mechanistic_narrative":"PF3D7_0204500 (AspAT) is a pyridoxal-5'-phosphate-dependent aspartate aminotransferase of P. falciparum that interconverts aspartate and α-ketoglutarate with oxaloacetate and glutamate and supplies aspartate for downstream biosynthesis [PMID:11443076, PMID:21209090]. The recombinant enzyme catalyzes aspartate–ketoglutarate, tyrosine–ketoglutarate, and amino acid–ketomethiobutyrate transaminations, and it performs the final transamination step of methionine regeneration from methylthioadenosine, albeit with ketomethiobutyrate turned over much more slowly than aspartate–ketoglutarate; canaline acts as an uncompetitive inhibitor (Ki 27 µM) [PMID:11443076]. Metabolically, AspAT operates downstream of the mitochondrial electron transport chain, converting fumarate-derived carbons (via malate and oxaloacetate) into aspartate that feeds nucleic acid and protein synthesis, a route abolished by the ETC inhibitor atovaquone [PMID:21209090]. The 2.8 Å crystal structure shows the enzyme is a cytosolic homodimer adopting the canonical AspAT fold but with a divergent N-terminal region; deletion of these N-terminal residues abolishes catalytic activity, and a peptide of the 13 divergent N-terminal residues inhibits the parasite enzyme in vitro and in lysates without affecting human cytosolic AspAT, marking this region as a basis for parasite-selective inhibition [PMID:21087616]. Notably, the P. falciparum enzyme lacks the residue G197 that is invariant across the Ia aminotransferase subfamily [PMID:11443076].","teleology":[{"year":2001,"claim":"Establishing the catalytic identity and substrate range of AspAT was the first step in defining its metabolic role, showing it is a broad-specificity aminotransferase that also completes methionine regeneration.","evidence":"recombinant expression with multi-substrate in vitro kinetic assays and inhibitor (canaline) characterization","pmids":["11443076"],"confidence":"High","gaps":["Relative in vivo importance of the methionine-regeneration versus aspartate-synthesis activities not resolved","Physiological significance of the missing G197 residue for catalysis not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Determining the enzyme was amenable to crystallization enabled subsequent structural analysis.","evidence":"recombinant purification, crystallization, and 2.8 Å X-ray diffraction data collection","pmids":["20383010"],"confidence":"Medium","gaps":["No structural interpretation yet at this stage","Superseded by the full structure determination"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"The crystal structure and N-terminal mutagenesis revealed that a divergent N-terminal region is essential for catalysis and offers a parasite-selective inhibition handle, and localized the enzyme to the cytosol.","evidence":"X-ray structure of the homodimer at 2.8 Å, N-terminal deletion, N-terminal peptide inhibition in vitro and in lysates, subcellular localization","pmids":["21087616"],"confidence":"High","gaps":["Mechanism by which the N-terminal peptide inhibits activity not resolved","No inhibitor developed from the N-terminal region against live parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Isotope tracing placed AspAT in a defined electron-transport-chain-dependent pathway that routes fumarate carbon into aspartate for nucleic acid and protein biosynthesis, giving the enzyme a concrete metabolic role in intraerythrocytic parasites.","evidence":"[2,3-14C] and [2,3-13C]fumarate labeling with NMR metabolite tracing and atovaquone inhibition in free parasites","pmids":["21209090"],"confidence":"High","gaps":["Genetic essentiality of AspAT for this pathway not tested","Direct enzymatic contribution inferred pharmacologically rather than by AspAT-specific perturbation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether AspAT is genetically essential and whether its N-terminal region can be exploited for a parasite-selective antimalarial in vivo remains open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic knockout/knockdown of AspAT in the corpus","No in vivo antimalarial validation of N-terminal-targeting inhibitors"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Homodimer"],"partners":[],"other_free_text":["PLP-dependent aspartate aminotransferase converting aspartate + α-ketoglutarate to oxaloacetate + glutamate [#0]","Catalyzes the final transamination step of methionine regeneration from methylthioadenosine [#0]","Lacks the G197 residue invariant across the Ia aminotransferase subfamily [#0]","Uncompetitively inhibited by canaline (Ki 27 µM) [#0]","Divergent N-terminal region essential for catalysis; a 13-residue N-terminal peptide inhibits the parasite enzyme without affecting human cytosolic AspAT [#1]","Operates downstream of the mitochondrial electron transport chain (malate quinone oxidoreductase), converting fumarate-derived carbon into aspartate for nucleic acid and protein synthesis; blocked by atovaquone [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"16492767","id":"PMC_16492767","title":"Aminoacyl-transferases and the N-end rule pathway of prokaryotic/eukaryotic specificity in a human pathogen.","date":"2006","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/16492767","citation_count":83,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AAT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21209090","id":"PMC_21209090","title":"Metabolic fate of fumarate, a side product of the purine salvage pathway in the intraerythrocytic stages of Plasmodium falciparum.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21209090","citation_count":53,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11443076","id":"PMC_11443076","title":"Methionine regeneration and aspartate aminotransferase in parasitic protozoa.","date":"2001","source":"Journal of bacteriology","url":"https://pubmed.ncbi.nlm.nih.gov/11443076","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21087616","id":"PMC_21087616","title":"Specific inhibition of the aspartate aminotransferase of Plasmodium falciparum.","date":"2010","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/21087616","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AspAT","aspartate aminotransferase","PfAspAT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28606087","id":"PMC_28606087","title":"Suppression of experimental cerebral malaria by disruption of malate:quinone oxidoreductase.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/28606087","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"386967","id":"PMC_386967","title":"Biochemistry of intraerythrocytic parasites. I. Identification of enzymes of parasite origin by starch-gel electrophoresis.","date":"1979","source":"Annals of tropical medicine and parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/386967","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24524072","id":"PMC_24524072","title":"Vitamin B6-dependent enzymes in the human malaria parasite Plasmodium falciparum: a druggable target?","date":"2014","source":"BioMed research international","url":"https://pubmed.ncbi.nlm.nih.gov/24524072","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AspAT","aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35711667","id":"PMC_35711667","title":"A Malaria Parasite Cross Reveals Genetic Determinants of Plasmodium falciparum Growth in Different Culture Media.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35711667","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate transaminase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22455555","id":"PMC_22455555","title":"Aspartate aminotransferase: bridging carbohydrate and energy metabolism in Plasmodium falciparum.","date":"2012","source":"Current drug metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/22455555","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["AspAT","aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20383010","id":"PMC_20383010","title":"Purification, crystallization and preliminary X-ray analysis of the aspartate aminotransferase of Plasmodium falciparum.","date":"2010","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/20383010","citation_count":11,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase","PfAspAT"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8773535","id":"PMC_8773535","title":"Studies on ammonia-metabolizing enzymes during Plasmodium yoelii infection and pyrimethamine treatment in mice.","date":"1996","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8773535","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate aminotransferase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1361009","id":"PMC_1361009","title":"Cerebral ammonia levels and enzyme changes during Plasmodium yoelii infection in mice.","date":"1992","source":"The Journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/1361009","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["aspartate transaminase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8754,"output_tokens":1489,"usd":0.024299,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6475,"output_tokens":2437,"usd":0.04665,"stage2_stop_reason":"end_turn"},"total_usd":0.070949,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"P. falciparum AspAT (PF3D7_0204500) was cloned, expressed as recombinant protein, and shown to catalyze aspartate-ketoglutarate, tyrosine-ketoglutarate, and amino acid-ketomethiobutyrate aminotransfer reactions in vitro. The P. falciparum enzyme is unique in lacking the invariant residue G197 conserved across the Ia subfamily of aminotransferases, and it catalyzes ketomethiobutyrate transamination significantly more slowly than aspartate-ketoglutarate aminotransfer. Canaline was identified as an uncompetitive inhibitor with a Ki of 27 µM. The enzyme was shown to function in the final step of methionine regeneration from methylthioadenosine.\",\n      \"method\": \"Recombinant protein expression, in vitro enzymatic assays with multiple substrates, kinetic analysis, inhibitor characterization\",\n      \"journal\": \"Journal of bacteriology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — recombinant enzyme reconstitution with multiple in vitro kinetic assays and inhibitor characterization in a single rigorous study\",\n      \"pmids\": [\"11443076\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PfAspAT (PF3D7_0204500) was crystallized and its X-ray structure solved as a homodimer at 2.8 Å resolution. The overall fold is similar to other AspATs but shows significant divergence in the conformation of the N-terminal residues. Deletion of these divergent N-terminal residues results in loss of catalytic activity for the recombinant protein. Addition of a peptide containing the 13 divergent N-terminal residues inhibits PfAspAT activity both in vitro and in parasite lysates, while leaving human cytosolic AspAT unaffected. The enzyme was localized to the parasite cytosol by direct experiment.\",\n      \"method\": \"X-ray crystallography (2.8 Å), N-terminal deletion mutagenesis, in vitro enzymatic activity assay, parasite lysate activity assay, subcellular localization\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure, active-site mutagenesis, and in vitro + in situ functional validation in one study\",\n      \"pmids\": [\"21087616\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In intraerythrocytic P. falciparum, fumarate (a side product of the purine salvage pathway) is converted to aspartate via malate and oxaloacetate. Isotope tracing with [2,3-14C]fumarate and [2,3-13C]fumarate showed incorporation into nucleic acid, protein, malate, and aspartate fractions. Treatment with atovaquone (an electron transport chain inhibitor) blocked the conversion of fumarate to aspartate, establishing that PfAspAT (aspartate aminotransferase) operates downstream of malate quinone oxidoreductase in an electron transport chain-dependent biosynthetic pathway supplying aspartate for nucleic acid and protein synthesis.\",\n      \"method\": \"Radioisotope labeling ([2,3-14C]fumarate), 13C NMR metabolite tracing, atovaquone inhibition experiment in free parasites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal isotope-tracing methods plus pharmacological pathway dissection in intact parasites, single lab\",\n      \"pmids\": [\"21209090\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"PfAspAT (PF3D7_0204500) was successfully expressed, purified to homogeneity, and crystallized, yielding a 2.8 Å diffraction dataset used for structure determination by molecular replacement, confirming the protein is amenable to structural analysis.\",\n      \"method\": \"Recombinant protein expression, purification, crystallization, X-ray diffraction data collection\",\n      \"journal\": \"Acta crystallographica. Section F, Structural biology and crystallization communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — structural crystallography report from single lab; preliminary findings superseded by the full structure paper (PMID 21087616)\",\n      \"pmids\": [\"20383010\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0204500 (AspAT) is a cytosolic homodimeric pyridoxal-5'-phosphate-dependent aspartate aminotransferase in P. falciparum whose 2.8 Å crystal structure reveals a divergent N-terminal region essential for catalytic activity; it converts aspartate and α-ketoglutarate to oxaloacetate and glutamate, operates downstream of the mitochondrial electron transport chain to channel fumarate-derived carbons into aspartate for nucleic acid and protein biosynthesis, and also catalyzes the final transamination step in methionine regeneration from methylthioadenosine, with its unique N-terminal residues offering a basis for parasite-selective inhibition.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0204500 (AspAT) is a pyridoxal-5'-phosphate-dependent aspartate aminotransferase of P. falciparum that interconverts aspartate and α-ketoglutarate with oxaloacetate and glutamate and supplies aspartate for downstream biosynthesis [#0, #2]. The recombinant enzyme catalyzes aspartate–ketoglutarate, tyrosine–ketoglutarate, and amino acid–ketomethiobutyrate transaminations, and it performs the final transamination step of methionine regeneration from methylthioadenosine, albeit with ketomethiobutyrate turned over much more slowly than aspartate–ketoglutarate; canaline acts as an uncompetitive inhibitor (Ki 27 µM) [#0]. Metabolically, AspAT operates downstream of the mitochondrial electron transport chain, converting fumarate-derived carbons (via malate and oxaloacetate) into aspartate that feeds nucleic acid and protein synthesis, a route abolished by the ETC inhibitor atovaquone [#2]. The 2.8 Å crystal structure shows the enzyme is a cytosolic homodimer adopting the canonical AspAT fold but with a divergent N-terminal region; deletion of these N-terminal residues abolishes catalytic activity, and a peptide of the 13 divergent N-terminal residues inhibits the parasite enzyme in vitro and in lysates without affecting human cytosolic AspAT, marking this region as a basis for parasite-selective inhibition [#1]. Notably, the P. falciparum enzyme lacks the residue G197 that is invariant across the Ia aminotransferase subfamily [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Establishing the catalytic identity and substrate range of AspAT was the first step in defining its metabolic role, showing it is a broad-specificity aminotransferase that also completes methionine regeneration.\",\n      \"evidence\": \"recombinant expression with multi-substrate in vitro kinetic assays and inhibitor (canaline) characterization\",\n      \"pmids\": [\"11443076\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Relative in vivo importance of the methionine-regeneration versus aspartate-synthesis activities not resolved\", \"Physiological significance of the missing G197 residue for catalysis not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Determining the enzyme was amenable to crystallization enabled subsequent structural analysis.\",\n      \"evidence\": \"recombinant purification, crystallization, and 2.8 Å X-ray diffraction data collection\",\n      \"pmids\": [\"20383010\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural interpretation yet at this stage\", \"Superseded by the full structure determination\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"The crystal structure and N-terminal mutagenesis revealed that a divergent N-terminal region is essential for catalysis and offers a parasite-selective inhibition handle, and localized the enzyme to the cytosol.\",\n      \"evidence\": \"X-ray structure of the homodimer at 2.8 Å, N-terminal deletion, N-terminal peptide inhibition in vitro and in lysates, subcellular localization\",\n      \"pmids\": [\"21087616\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which the N-terminal peptide inhibits activity not resolved\", \"No inhibitor developed from the N-terminal region against live parasites\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Isotope tracing placed AspAT in a defined electron-transport-chain-dependent pathway that routes fumarate carbon into aspartate for nucleic acid and protein biosynthesis, giving the enzyme a concrete metabolic role in intraerythrocytic parasites.\",\n      \"evidence\": \"[2,3-14C] and [2,3-13C]fumarate labeling with NMR metabolite tracing and atovaquone inhibition in free parasites\",\n      \"pmids\": [\"21209090\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genetic essentiality of AspAT for this pathway not tested\", \"Direct enzymatic contribution inferred pharmacologically rather than by AspAT-specific perturbation\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether AspAT is genetically essential and whether its N-terminal region can be exploited for a parasite-selective antimalarial in vivo remains open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No genetic knockout/knockdown of AspAT in the corpus\", \"No in vivo antimalarial validation of N-terminal-targeting inhibitors\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004069\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0030170\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0016769\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006531\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0019509\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Homodimer\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"PLP-dependent aspartate aminotransferase converting aspartate + α-ketoglutarate to oxaloacetate + glutamate [#0]\",\n      \"Catalyzes the final transamination step of methionine regeneration from methylthioadenosine [#0]\",\n      \"Lacks the G197 residue invariant across the Ia aminotransferase subfamily [#0]\",\n      \"Uncompetitively inhibited by canaline (Ki 27 µM) [#0]\",\n      \"Divergent N-terminal region essential for catalysis; a 13-residue N-terminal peptide inhibits the parasite enzyme without affecting human cytosolic AspAT [#1]\",\n      \"Operates downstream of the mitochondrial electron transport chain (malate quinone oxidoreductase), converting fumarate-derived carbon into aspartate for nucleic acid and protein synthesis; blocked by atovaquone [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0204500","name":null,"product":"aspartate transaminase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0302300","name":null,"product":"aspartate aminotransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0416400","name":null,"product":"aspartate aminotransferase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AAT","evaluation":null}