{"gene":"PF3D7_1411600","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2018,"finding":"Obg1 (PF3D7_1411600) localizes to the mitochondrion of P. falciparum, as demonstrated by direct localization experiments.","method":"Subcellular fractionation / fluorescence localization (direct localization experiment)","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional follow-up in a single lab study","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Obg1 (PF3D7_1411600) interacts with P. falciparum mitoribosomes in vivo, as shown by co-immunoprecipitation; this interaction is independent of nucleotide binding.","method":"Co-immunoprecipitation (in vivo)","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with nucleotide-independence tested, single lab","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Obg1 (PF3D7_1411600) possesses GTPase activity that is enhanced upon ribosomal association, establishing a mechanistic link between ribosome binding and stimulation of GTP hydrolysis.","method":"In vitro GTPase activity assay with and without ribosomes","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro enzymatic assay with ribosome stimulation tested, single lab","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Obg1 (PF3D7_1411600) specifically interacts with the P. falciparum mitochondrial genome in vivo, and deletion analysis revealed that the positively-charged OBG domain mediates this DNA-binding activity.","method":"In vivo DNA interaction assay; deletion analysis of OBG domain","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain deletion analysis combined with in vivo DNA-binding assay, single lab","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Obg1 (PF3D7_1411600) is implicated in mitochondrial ribosome assembly in P. falciparum, with PfEngA, Obg1, and PfYihA2 together inferred to aid mitochondrial ribosome biogenesis based on combined co-immunoprecipitation and localization evidence.","method":"Co-immunoprecipitation; subcellular localization (cited as prior report in context of new YihA study)","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — cited as contextual prior finding in a single lab paper, no new direct experiment on Obg1 itself","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"Obg1 (PF3D7_1411600) is a mitochondrion-localized GTP-binding protein in P. falciparum that interacts with mitoribosomes in a nucleotide-independent manner, exhibits ribosome-stimulated GTPase activity, and binds the mitochondrial genome via its positively-charged OBG domain, collectively supporting a role in mitochondrial ribosome assembly and mitochondrial DNA transactions."},"narrative":{"mechanistic_narrative":"Obg1 (PF3D7_1411600) is a mitochondrion-localized GTP-binding protein of P. falciparum that couples GTP hydrolysis to mitochondrial ribosome function and mitochondrial genome binding [PMID:29642957]. It associates with mitoribosomes in vivo in a nucleotide-independent manner, and this ribosomal association stimulates its intrinsic GTPase activity, linking ribosome engagement to GTP turnover [PMID:29642957]. Obg1 also binds the P. falciparum mitochondrial genome in vivo through its positively-charged OBG domain, as defined by domain-deletion analysis [PMID:29642957]. Together these activities are consistent with a role in mitochondrial ribosome assembly and mitochondrial DNA transactions [PMID:32057832]. Beyond these findings from a single body of work, no further mechanistic detail on Obg1 has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where Obg1 acts was the first step: direct localization placed the protein in the parasite mitochondrion, defining the organelle in which its GTP-binding activity operates.","evidence":"Subcellular fractionation / fluorescence localization in P. falciparum","pmids":["29642957"],"confidence":"Medium","gaps":["Does not resolve submitochondrial distribution (matrix vs. membrane association)","Single lab study without independent confirmation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To connect Obg1 to a molecular machine, co-immunoprecipitation showed it binds mitoribosomes in vivo, and the interaction was shown to be nucleotide-independent, indicating ribosome contact does not require prior GTP loading.","evidence":"In vivo co-immunoprecipitation with nucleotide-independence tested, P. falciparum","pmids":["29642957"],"confidence":"Medium","gaps":["Which ribosomal subunit or protein Obg1 contacts is not defined","No reciprocal validation reported","Whether the interaction is direct or bridged by other factors is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To test whether ribosome binding is functionally meaningful, in vitro GTPase assays showed that ribosomal association enhances Obg1 GTP hydrolysis, establishing the ribosome as an activator of its enzymatic cycle.","evidence":"In vitro GTPase activity assay with and without ribosomes, P. falciparum","pmids":["29642957"],"confidence":"Medium","gaps":["Kinetic parameters and the structural basis of stimulation are not defined","Downstream consequence of GTP hydrolysis on the ribosome is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To probe a second potential substrate, in vivo DNA-interaction and domain-deletion analysis showed Obg1 binds the mitochondrial genome via its positively-charged OBG domain, mapping the nucleic-acid-binding activity to a defined region.","evidence":"In vivo DNA interaction assay with OBG-domain deletion analysis, P. falciparum","pmids":["29642957"],"confidence":"Medium","gaps":["Sequence specificity of mtDNA binding is not defined","Functional consequence of mtDNA binding for genome maintenance or expression is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Placing Obg1 in a broader assembly framework, it was inferred alongside PfEngA and PfYihA2 to contribute to mitochondrial ribosome biogenesis, integrating the earlier ribosome and localization data into a pathway hypothesis.","evidence":"Co-IP and localization cited as prior context within a YihA study; no new direct experiment on Obg1, P. falciparum","pmids":["32057832"],"confidence":"Low","gaps":["Contextual citation only — no new direct experiment on Obg1 in this work","The specific step of ribosome assembly Obg1 acts on is not defined","Functional interdependence of the three GTPases is not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether Obg1 GTP hydrolysis is mechanistically required for a defined step of mitoribosome maturation, and how its mtDNA-binding and ribosome-binding activities are coordinated in the mitochondrion, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No loss-of-function phenotype for Obg1 characterized in the corpus","No structural model of the Obg1–ribosome or Obg1–mtDNA complex","Essentiality and drug-target potential not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MITORIBOSOME (MITOCHONDRIAL RIBOSOME) [#1, #2]","P. FALCIPARUM MITOCHONDRIAL GENOME (MTDNA) [#3]"],"other_free_text":["Interaction with mitoribosomes is nucleotide-independent [#1].","GTPase activity is stimulated by ribosomal association [#2].","mtDNA binding is mediated by the positively-charged OBG domain, as defined by deletion analysis [#3].","Grouped with PfEngA and PfYihA2 as GTPases inferred to aid mitochondrial ribosome biogenesis; this 2020 assignment is a contextual citation, not a new experiment on Obg1 [#4]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18174226","id":"PMC_18174226","title":"Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation.","date":"2008","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/18174226","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"29642957","id":"PMC_29642957","title":"Characterization of mitochondrion-targeted GTPases in Plasmodium falciparum.","date":"2018","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/29642957","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP","PfObg1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36945434","id":"PMC_36945434","title":"Functional profiling of the Toxoplasma genome during acute mouse infection.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36945434","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"32057832","id":"PMC_32057832","title":"YihA GTPases localize to the apicoplast and mitochondrion of the malaria parasite and interact with LSU of organellar ribosomes.","date":"2020","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/32057832","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfObg1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4830,"output_tokens":1151,"usd":0.015877,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5982,"output_tokens":2516,"usd":0.046405,"stage2_stop_reason":"end_turn"},"total_usd":0.062282,"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\": 2018,\n      \"finding\": \"Obg1 (PF3D7_1411600) localizes to the mitochondrion of P. falciparum, as demonstrated by direct localization experiments.\",\n      \"method\": \"Subcellular fractionation / fluorescence localization (direct localization experiment)\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional follow-up in a single lab study\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Obg1 (PF3D7_1411600) interacts with P. falciparum mitoribosomes in vivo, as shown by co-immunoprecipitation; this interaction is independent of nucleotide binding.\",\n      \"method\": \"Co-immunoprecipitation (in vivo)\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with nucleotide-independence tested, single lab\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Obg1 (PF3D7_1411600) possesses GTPase activity that is enhanced upon ribosomal association, establishing a mechanistic link between ribosome binding and stimulation of GTP hydrolysis.\",\n      \"method\": \"In vitro GTPase activity assay with and without ribosomes\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro enzymatic assay with ribosome stimulation tested, single lab\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Obg1 (PF3D7_1411600) specifically interacts with the P. falciparum mitochondrial genome in vivo, and deletion analysis revealed that the positively-charged OBG domain mediates this DNA-binding activity.\",\n      \"method\": \"In vivo DNA interaction assay; deletion analysis of OBG domain\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain deletion analysis combined with in vivo DNA-binding assay, single lab\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Obg1 (PF3D7_1411600) is implicated in mitochondrial ribosome assembly in P. falciparum, with PfEngA, Obg1, and PfYihA2 together inferred to aid mitochondrial ribosome biogenesis based on combined co-immunoprecipitation and localization evidence.\",\n      \"method\": \"Co-immunoprecipitation; subcellular localization (cited as prior report in context of new YihA study)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — cited as contextual prior finding in a single lab paper, no new direct experiment on Obg1 itself\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Obg1 (PF3D7_1411600) is a mitochondrion-localized GTP-binding protein in P. falciparum that interacts with mitoribosomes in a nucleotide-independent manner, exhibits ribosome-stimulated GTPase activity, and binds the mitochondrial genome via its positively-charged OBG domain, collectively supporting a role in mitochondrial ribosome assembly and mitochondrial DNA transactions.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Obg1 (PF3D7_1411600) is a mitochondrion-localized GTP-binding protein of P. falciparum that couples GTP hydrolysis to mitochondrial ribosome function and mitochondrial genome binding [#0, #2]. It associates with mitoribosomes in vivo in a nucleotide-independent manner, and this ribosomal association stimulates its intrinsic GTPase activity, linking ribosome engagement to GTP turnover [#1, #2]. Obg1 also binds the P. falciparum mitochondrial genome in vivo through its positively-charged OBG domain, as defined by domain-deletion analysis [#3]. Together these activities are consistent with a role in mitochondrial ribosome assembly and mitochondrial DNA transactions [#4]. Beyond these findings from a single body of work, no further mechanistic detail on Obg1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where Obg1 acts was the first step: direct localization placed the protein in the parasite mitochondrion, defining the organelle in which its GTP-binding activity operates.\",\n      \"evidence\": \"Subcellular fractionation / fluorescence localization in P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Does not resolve submitochondrial distribution (matrix vs. membrane association)\",\n        \"Single lab study without independent confirmation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To connect Obg1 to a molecular machine, co-immunoprecipitation showed it binds mitoribosomes in vivo, and the interaction was shown to be nucleotide-independent, indicating ribosome contact does not require prior GTP loading.\",\n      \"evidence\": \"In vivo co-immunoprecipitation with nucleotide-independence tested, P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Which ribosomal subunit or protein Obg1 contacts is not defined\",\n        \"No reciprocal validation reported\",\n        \"Whether the interaction is direct or bridged by other factors is unresolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To test whether ribosome binding is functionally meaningful, in vitro GTPase assays showed that ribosomal association enhances Obg1 GTP hydrolysis, establishing the ribosome as an activator of its enzymatic cycle.\",\n      \"evidence\": \"In vitro GTPase activity assay with and without ribosomes, P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Kinetic parameters and the structural basis of stimulation are not defined\",\n        \"Downstream consequence of GTP hydrolysis on the ribosome is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To probe a second potential substrate, in vivo DNA-interaction and domain-deletion analysis showed Obg1 binds the mitochondrial genome via its positively-charged OBG domain, mapping the nucleic-acid-binding activity to a defined region.\",\n      \"evidence\": \"In vivo DNA interaction assay with OBG-domain deletion analysis, P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Sequence specificity of mtDNA binding is not defined\",\n        \"Functional consequence of mtDNA binding for genome maintenance or expression is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Placing Obg1 in a broader assembly framework, it was inferred alongside PfEngA and PfYihA2 to contribute to mitochondrial ribosome biogenesis, integrating the earlier ribosome and localization data into a pathway hypothesis.\",\n      \"evidence\": \"Co-IP and localization cited as prior context within a YihA study; no new direct experiment on Obg1, P. falciparum\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Contextual citation only \\u2014 no new direct experiment on Obg1 in this work\",\n        \"The specific step of ribosome assembly Obg1 acts on is not defined\",\n        \"Functional interdependence of the three GTPases is not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether Obg1 GTP hydrolysis is mechanistically required for a defined step of mitoribosome maturation, and how its mtDNA-binding and ribosome-binding activities are coordinated in the mitochondrion, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function phenotype for Obg1 characterized in the corpus\",\n        \"No structural model of the Obg1\\u2013ribosome or Obg1\\u2013mtDNA complex\",\n        \"Essentiality and drug-target potential not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0005525\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0043022\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000154\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0042255\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"mitoribosome (mitochondrial ribosome) [#1, #2]\",\n      \"P. falciparum mitochondrial genome (mtDNA) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Interaction with mitoribosomes is nucleotide-independent [#1].\",\n      \"GTPase activity is stimulated by ribosomal association [#2].\",\n      \"mtDNA binding is mediated by the positively-charged OBG domain, as defined by deletion analysis [#3].\",\n      \"Grouped with PfEngA and PfYihA2 as GTPases inferred to aid mitochondrial ribosome biogenesis; this 2020 assignment is a contextual citation, not a new experiment on Obg1 [#4].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1411600","name":null,"product":"GTP-binding protein Obg1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1030900","name":null,"product":"GTP-binding protein Obg1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1346700","name":null,"product":"GTP-binding protein Obg1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"Obg1","evaluation":null}