{"gene":"PF3D7_1436000","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":1990,"finding":"The P. falciparum glucose-6-phosphate isomerase gene (GPI; PF3D7_1436000) was isolated by genetic complementation of an E. coli double mutant lacking glucose phosphate isomerase. The gene contains a 1773-bp open reading frame with no introns, maps to P. falciparum chromosome 14, and encodes a functional enzyme with 34% amino acid identity to human glucose phosphate isomerase, with highest similarity in regions of the proposed active sites. The putative translation initiation site was determined by deletional and site-directed mutagenesis.","method":"Genetic complementation in E. coli, gene cloning, sequencing, deletional and oligonucleotide-mediated site-specific mutagenesis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation confirmed enzymatic activity, initiation site confirmed by mutagenesis, single lab with two orthogonal methods","pmids":["2197273"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1436000 (GPI) encodes a functional glucose-6-phosphate isomerase that is expressed from a 1773-bp intronless open reading frame on chromosome 14 of P. falciparum, shares ~34% amino acid identity with the human enzyme (with conservation highest at proposed active sites), and produces an active enzyme capable of complementing glucose phosphate isomerase-deficient E. coli mutants."},"narrative":{"mechanistic_narrative":"PF3D7_1436000 (GPI) encodes a functional glucose-6-phosphate isomerase of Plasmodium falciparum, isolated by genetic complementation of an E. coli double mutant lacking glucose phosphate isomerase, demonstrating that the encoded protein is catalytically active [PMID:2197273]. The gene comprises a 1773-bp intronless open reading frame on chromosome 14, with its translation initiation site defined by deletional and site-directed mutagenesis, and shares ~34% amino acid identity with the human enzyme, the conservation being highest in regions corresponding to the proposed active sites [PMID:2197273]. Beyond this initial identification and functional confirmation [PMID:2197273], no further mechanistic detail on PF3D7_1436000 has been characterized in the available corpus.","teleology":[{"year":1990,"claim":"Whether P. falciparum encodes a functional glucose-6-phosphate isomerase was unknown; complementation of a glucose phosphate isomerase-deficient E. coli mutant established that this gene produces a catalytically active enzyme.","evidence":"Genetic complementation in E. coli, gene cloning and sequencing, with deletional and oligonucleotide-mediated site-specific mutagenesis to define the initiation site","pmids":["2197273"],"confidence":"Medium","gaps":["No structural model or biochemical kinetic characterization of the P. falciparum enzyme","The enzyme's role in parasite glycolysis or its essentiality in vivo was not tested","No inhibitor or drug-target validation reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PF3D7_1436000 functions within P. falciparum metabolism, its localization, regulation, and essentiality during the parasite life cycle remain uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No subcellular localization determined","No genetic knockout or essentiality data in the parasite","No interaction partners or pathway context established beyond inferred glycolytic activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["1773-bp intronless open reading frame on P. falciparum chromosome 14 [#0]","~34% amino acid identity to human glucose phosphate isomerase, highest at proposed active sites [#0]","Enzymatic activity confirmed by complementation of a glucose phosphate isomerase-deficient E. coli double mutant [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"10455162","id":"PMC_10455162","title":"The protozoan parasite Toxoplasma gondii expresses two functional plant-like glycolytic enzymes. Implications for evolutionary origin of apicomplexans.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10455162","citation_count":86,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["glucose-6-phosphate isomerase"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"7029800","id":"PMC_7029800","title":"Enzyme typing of Plasmodium falciparum from African and some other Old World countries.","date":"1981","source":"Transactions of the Royal Society of Tropical Medicine and Hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/7029800","citation_count":80,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"6370002","id":"PMC_6370002","title":"Drug sensitivity and isoenzyme type in cloned lines of Plasmodium falciparum.","date":"1984","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/6370002","citation_count":64,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"3914841","id":"PMC_3914841","title":"Cloning and characterization of mefloquine-resistant Plasmodium falciparum from Thailand.","date":"1985","source":"The American journal of tropical medicine and hygiene","url":"https://pubmed.ncbi.nlm.nih.gov/3914841","citation_count":55,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2197273","id":"PMC_2197273","title":"Cloning metabolic pathway genes by complementation in Escherichia coli. Isolation and expression of Plasmodium falciparum glucose phosphate isomerase.","date":"1990","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2197273","citation_count":37,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41977140","id":"PMC_41977140","title":"Anti-GPI scFv as a Promising Tool for Intervention Against Cerebral Malaria in Mice.","date":"2026","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41977140","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40832631","id":"PMC_40832631","title":"mRNA-LNP vaccine encoding the Plasmodium vivax circumsporozoite protein is highly immunogenic and confers protection in mice.","date":"2025","source":"Molecular therapy. Nucleic acids","url":"https://pubmed.ncbi.nlm.nih.gov/40832631","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40608817","id":"PMC_40608817","title":"Hexosamine biosynthesis disruption impairs GPI production and arrests Plasmodium falciparum growth at schizont stages.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/40608817","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41373744","id":"PMC_41373744","title":"Free GPIs and Comparison of GPI Structures Among Species.","date":"2025","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/41373744","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38262838","id":"PMC_38262838","title":"Glycosylation in malaria parasites: what do we know?","date":"2024","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/38262838","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39002668","id":"PMC_39002668","title":"The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane.","date":"2024","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/39002668","citation_count":10,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39241090","id":"PMC_39241090","title":"Apicoplast-derived isoprenoids are essential for biosynthesis of GPI protein anchors, and consequently for egress and invasion in Plasmodium falciparum.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39241090","citation_count":8,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38826328","id":"PMC_38826328","title":"The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/38826328","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36698187","id":"PMC_36698187","title":"FT-GPI, a highly sensitive and accurate predictor of GPI-anchored proteins, reveals the composition and evolution of the GPI proteome in Plasmodium species.","date":"2023","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/36698187","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35222844","id":"PMC_35222844","title":"Compounds targeting GPI biosynthesis or N-glycosylation are active against Plasmodium falciparum.","date":"2022","source":"Computational and structural biotechnology journal","url":"https://pubmed.ncbi.nlm.nih.gov/35222844","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GPI"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9444,"output_tokens":855,"usd":0.020578,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4977,"output_tokens":1127,"usd":0.02653,"stage2_stop_reason":"end_turn"},"total_usd":0.047108,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"I need to carefully evaluate each paper to determine if it is about PF3D7_1436000 (glucose-6-phosphate isomerase, GPI) in Plasmodium, or about glycosylphosphatidylinositol (GPI) anchors/biosynthesis, which shares the abbreviation \"GPI\" but is a completely different biological entity.\n\nPF3D7_1436000 is the **glucose-6-phosphate isomerase** enzyme (also called phosphoglucose isomerase), which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate in glycolysis.\n\nPapers 6-15 all appear to be about **glycosylphosphatidylinositol (GPI) anchors** — a lipid anchor modification — NOT about glucose-6-phosphate isomerase. These must be excluded.\n\nPapers 1-5 use \"GPI\" or \"G6-PI\" in context of glucose-6-phosphate isomerase:\n- Paper 1: About T. gondii G6-PI (and Plasmodium falciparum mentioned in phylogeny/3D models) — the Plasmodium findings are limited to phylogenetic modeling, not direct experiments on PF3D7_1436000.\n- Paper 2: Enzyme typing using GPI electrophoresis — population genetics, not mechanistic.\n- Paper 3: GPI isoenzyme typing of clones — population genetics, not mechanistic.\n- Paper 4: GPI isoenzyme typing — population genetics, not mechanistic.\n- Paper 5: Direct cloning and expression of P. falciparum glucose phosphate isomerase — this IS about PF3D7_1436000 and contains mechanistic findings.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1990,\n      \"finding\": \"The P. falciparum glucose-6-phosphate isomerase gene (GPI; PF3D7_1436000) was isolated by genetic complementation of an E. coli double mutant lacking glucose phosphate isomerase. The gene contains a 1773-bp open reading frame with no introns, maps to P. falciparum chromosome 14, and encodes a functional enzyme with 34% amino acid identity to human glucose phosphate isomerase, with highest similarity in regions of the proposed active sites. The putative translation initiation site was determined by deletional and site-directed mutagenesis.\",\n      \"method\": \"Genetic complementation in E. coli, gene cloning, sequencing, deletional and oligonucleotide-mediated site-specific mutagenesis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation confirmed enzymatic activity, initiation site confirmed by mutagenesis, single lab with two orthogonal methods\",\n      \"pmids\": [\"2197273\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1436000 (GPI) encodes a functional glucose-6-phosphate isomerase that is expressed from a 1773-bp intronless open reading frame on chromosome 14 of P. falciparum, shares ~34% amino acid identity with the human enzyme (with conservation highest at proposed active sites), and produces an active enzyme capable of complementing glucose phosphate isomerase-deficient E. coli mutants.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1436000 (GPI) encodes a functional glucose-6-phosphate isomerase of Plasmodium falciparum, isolated by genetic complementation of an E. coli double mutant lacking glucose phosphate isomerase, demonstrating that the encoded protein is catalytically active [#0]. The gene comprises a 1773-bp intronless open reading frame on chromosome 14, with its translation initiation site defined by deletional and site-directed mutagenesis, and shares ~34% amino acid identity with the human enzyme, the conservation being highest in regions corresponding to the proposed active sites [#0]. Beyond this initial identification and functional confirmation [#0], no further mechanistic detail on PF3D7_1436000 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Whether P. falciparum encodes a functional glucose-6-phosphate isomerase was unknown; complementation of a glucose phosphate isomerase-deficient E. coli mutant established that this gene produces a catalytically active enzyme.\",\n      \"evidence\": \"Genetic complementation in E. coli, gene cloning and sequencing, with deletional and oligonucleotide-mediated site-specific mutagenesis to define the initiation site\",\n      \"pmids\": [\"2197273\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or biochemical kinetic characterization of the P. falciparum enzyme\",\n        \"The enzyme's role in parasite glycolysis or its essentiality in vivo was not tested\",\n        \"No inhibitor or drug-target validation reported\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PF3D7_1436000 functions within P. falciparum metabolism, its localization, regulation, and essentiality during the parasite life cycle remain uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No subcellular localization determined\",\n        \"No genetic knockout or essentiality data in the parasite\",\n        \"No interaction partners or pathway context established beyond inferred glycolytic activity\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004347\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"1773-bp intronless open reading frame on P. falciparum chromosome 14 [#0]\",\n      \"~34% amino acid identity to human glucose phosphate isomerase, highest at proposed active sites [#0]\",\n      \"Enzymatic activity confirmed by complementation of a glucose phosphate isomerase-deficient E. coli double mutant [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1436000","name":null,"product":"glucose-6-phosphate isomerase","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1008800","name":null,"product":"glucose-6-phosphate isomerase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0422600","name":null,"product":"glucose-6-phosphate isomerase","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"GPI","evaluation":null}