{"gene":"PF3D7_1120100","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2022,"finding":"PfPGM1 (PF3D7_1120100) forms a tetramer that is critical for optimal enzymatic activity in vivo; single point mutation W68A abolishes tetramerization and drastically reduces catalytic activity in vitro, while mutation of the conserved residue K100 also leads to drastic reduction in enzymatic activity. Conditional knockdown demonstrated PfPGM1 is essential for intraerythrocytic parasite survival. Ectopic expression of wild-type PfPGM1 enhanced parasite growth, whereas the monomeric (W68) mutant form failed to provide growth advantage.","method":"Site-directed mutagenesis, in vitro enzymatic assay, conditional knockdown (loss-of-function), ectopic overexpression with parasite growth readout","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — in vitro mutagenesis + enzymatic assay combined with in vivo conditional knockdown and growth complementation, multiple orthogonal methods in a single rigorous study","pmids":["35150741"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"PfPGM1 (PF3D7_1120100) is post-translationally regulated by lysine acetylation: the catalytic residue K100 is acetylated by the essential histone acetyltransferase PfGCN5. Acetylation modulates PfPGM1 protein stability rather than directly altering catalytic activity (increasing the protein pool). Additionally, PfGCN5 occupies the PfPGM1 promoter in a stage-specific manner, and knockdown of PfGCN5 reduces PfPGM1 transcript levels, revealing dual regulation (post-translational protein stability and transcriptional control) of PfPGM1 by PfGCN5.","method":"Knockdown of PfGCN5 + cycloheximide chase (protein stability assay), ChIP (PfGCN5 promoter occupancy), RT-qPCR (transcript level), in vitro acetyltransferase assay, site-directed mutagenesis (K100)","journal":"The FEBS journal","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — multiple orthogonal methods (ChIP, cycloheximide chase, in vitro acetyltransferase assay, mutagenesis) in a single focused study on PfPGM1","pmids":["40567037"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Phosphoglycerate mutase (PfPGM1/PF3D7_1120100) was identified as a target of protein S-glutathionylation in P. falciparum using enzymatic deglutathionylation, biotin-maleimide affinity purification, and proteomic analysis, indicating it can form a mixed disulfide with glutathione as a redox-sensitive post-translational modification.","method":"Enzymatic deglutathionylation, affinity purification (biotin-maleimide), proteomics/mass spectrometry","journal":"Antioxidants & redox signaling","confidence":"Low","confidence_rationale":"Tier 3 / Weak — identified in a proteome-wide screen; no functional follow-up specific to PfPGM1 activity reported in this abstract","pmids":["21595565"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Phosphoglycerate mutase (PF3D7_1120100) was captured as a target of cytosolic thioredoxin 1 (PfTrx-1) in P. falciparum using a cysteine-mutant Trx affinity chromatography approach, identifying it as a substrate in the thioredoxin reduction pathway.","method":"Trx-affinity chromatography (cysteine mutant C33S trap), LC-MS/MS","journal":"Parasitology international","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single affinity pulldown/MS identification; no functional follow-up specific to PfPGM1 reported in this abstract","pmids":["20307687"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Structural and enzymatic comparison established that PfPGM1 (PF3D7_1120100) and PfPGM2 (a paralog) have distinct catalytic conformations; PfPGM1 was used as a reference for sequence/structural comparison, while the characterized PfPGM2 acts primarily as a phosphatase with only residual mutase activity. The two P. falciparum PGMase-family proteins thus have functionally divergent enzymatic activities.","method":"Crystal structure determination (of PfPGM2), sequence and structural comparison with PfPGM1, in vitro enzymatic activity assay","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — structural and enzymatic work was performed on PfPGM2 and Cryptosporidium PGM; PfPGM1 was used only for comparative sequence/structural analysis without direct enzymatic characterization of PfPGM1 itself","pmids":["21689687"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfPGM1 (PF3D7_1120100) is an essential glycolytic phosphoglycerate mutase in P. falciparum that functions as a tetramer—tetramerization via residue W68 and catalytic activity via residue K100 are both required for optimal enzymatic function and parasite growth; K100 is acetylated by the acetyltransferase PfGCN5, which modulates PfPGM1 protein stability, while PfGCN5 also transcriptionally controls PfPGM1 expression through stage-specific promoter occupancy, and PfPGM1 can additionally be S-glutathionylated and is a substrate of thioredoxin 1 as part of broader redox regulation in the parasite."},"narrative":{"mechanistic_narrative":"PGM1 (PF3D7_1120100) is an essential phosphoglycerate mutase required for intraerythrocytic survival of Plasmodium falciparum [PMID:35150741]. It functions as a tetramer: the residue W68 mediates oligomerization, and its mutation to alanine abolishes tetramer formation and drastically reduces catalytic activity in vitro, while the conserved residue K100 is likewise required for enzymatic activity [PMID:35150741]. Consistent with an essential metabolic role, conditional knockdown impairs parasite growth and ectopic wild-type expression enhances growth, whereas the monomeric W68 mutant confers no growth advantage [PMID:35150741]. PGM1 is subject to dual control by the acetyltransferase PfGCN5: PfGCN5 acetylates the catalytic K100 residue to increase PGM1 protein stability and pool size rather than to directly alter catalytic rate, and PfGCN5 also occupies the PGM1 promoter in a stage-specific manner such that its knockdown lowers PGM1 transcript levels [PMID:40567037]. Beyond these established regulatory and structural features, PGM1 has been captured in redox-proteomic screens as a target of S-glutathionylation and as a substrate of cytosolic thioredoxin 1, though no PGM1-specific functional consequence of these modifications has been characterized in the available corpus [PMID:21595565, PMID:20307687].","teleology":[{"year":2010,"claim":"To place PGM1 within the parasite's redox network, it was asked whether the enzyme is a substrate of the thioredoxin reduction pathway.","evidence":"Trx-affinity chromatography using a cysteine-mutant (C33S) trap with LC-MS/MS identification","pmids":["20307687"],"confidence":"Low","gaps":["Single affinity pulldown/MS identification with no functional follow-up on PGM1 activity","Which cysteine residues are targeted is not defined","The physiological consequence of thioredoxin reduction of PGM1 is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Redox-proteomic screening asked whether PGM1 undergoes reversible thiol modification, testing whether it can form a mixed disulfide with glutathione.","evidence":"Enzymatic deglutathionylation with biotin-maleimide affinity purification and proteomic mass spectrometry","pmids":["21595565"],"confidence":"Low","gaps":["Proteome-wide identification without PGM1-specific functional validation","Effect of S-glutathionylation on catalytic activity or tetramerization not tested","Modified residues not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"To determine whether the two P. falciparum PGMase-family proteins are functionally redundant, PGM1 was compared structurally and enzymatically against its paralog PfPGM2.","evidence":"Crystal structure of PfPGM2, sequence/structural comparison with PGM1, and in vitro enzymatic assays","pmids":["21689687"],"confidence":"Low","gaps":["Direct enzymatic characterization was performed on PfPGM2, not PGM1; PGM1 served only as a comparative reference","No structure of PGM1 itself was determined","The distinct catalytic conformation of PGM1 is inferred, not experimentally solved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"The central question of PGM1's essentiality and the structural basis of its activity was resolved by linking tetramerization and specific catalytic residues to enzyme function and parasite growth.","evidence":"Site-directed mutagenesis (W68A, K100) with in vitro enzymatic assays, conditional knockdown, and ectopic overexpression growth complementation","pmids":["35150741"],"confidence":"High","gaps":["Structure of the PGM1 tetramer not solved","Whether K100 contributes to catalysis directly or to substrate binding is not resolved","Metabolic flux consequences of knockdown not quantified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"How PGM1 abundance is controlled was addressed by identifying PfGCN5 as a dual regulator acting at both the protein-stability and transcriptional levels.","evidence":"PfGCN5 knockdown with cycloheximide chase, ChIP for promoter occupancy, RT-qPCR, in vitro acetyltransferase assay, and K100 mutagenesis","pmids":["40567037"],"confidence":"High","gaps":["Stoichiometry and dynamics of K100 acetylation in vivo not quantified","The deacetylase counteracting PfGCN5 on PGM1 is unidentified","How acetylation at the catalytic K100 stabilizes protein without altering activity is mechanistically unexplained"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether the redox modifications (S-glutathionylation, thioredoxin reduction) integrate with acetylation and tetramerization to coordinately regulate PGM1 function during the parasite life cycle.","evidence":"","pmids":[],"confidence":"Low","gaps":["No functional link established between redox modifications and PGM1 catalytic output","No structural model of the PGM1 tetramer","Cross-talk between transcriptional, acetylation, and redox control of PGM1 not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PGM1 homotetramer (tetramerization dependent on residue W68)"],"partners":["PFGCN5 (HISTONE ACETYLTRANSFERASE; ACETYLATES PGM1 K100 AND CONTROLS PGM1 TRANSCRIPTION)","CYTOSOLIC THIOREDOXIN 1 (PFTRX-1; PGM1 IS A SUBSTRATE)"],"other_free_text":["Essential for intraerythrocytic P. falciparum survival (conditional knockdown loss-of-function).","Catalytic residue K100 required for activity and is the site of PfGCN5-mediated acetylation, which increases protein stability rather than catalytic rate.","Identified as a target of protein S-glutathionylation in redox proteomics.","Paralog PfPGM2 has divergent enzymatic activity (primarily phosphatase); PGM1 served as comparative reference in that structural study."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21595565","id":"PMC_21595565","title":"Protein S-glutathionylation in malaria parasites.","date":"2011","source":"Antioxidants & redox signaling","url":"https://pubmed.ncbi.nlm.nih.gov/21595565","citation_count":87,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21689687","id":"PMC_21689687","title":"Characterization of a new phosphatase from Plasmodium.","date":"2011","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/21689687","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase","PfPGM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"23339668","id":"PMC_23339668","title":"PfHPRT: a new biomarker candidate of acute Plasmodium falciparum infection.","date":"2013","source":"Journal of proteome research","url":"https://pubmed.ncbi.nlm.nih.gov/23339668","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20307687","id":"PMC_20307687","title":"Target proteins of the cytosolic thioredoxin in Plasmodium falciparum.","date":"2010","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/20307687","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35150741","id":"PMC_35150741","title":"The tetrameric structure of Plasmodium falciparum phosphoglycerate mutase is critical for optimal enzymatic activity.","date":"2022","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35150741","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase","PfPGM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25183269","id":"PMC_25183269","title":"Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.","date":"2014","source":"Asian Pacific journal of tropical biomedicine","url":"https://pubmed.ncbi.nlm.nih.gov/25183269","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30370850","id":"PMC_30370850","title":"Virtual Screening, Molecular Dynamics and ADME-Tox Tools for Finding Potential Inhibitors of Phosphoglycerate Mutase 1 from Plasmodium falciparum.","date":"2018","source":"Current topics in medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/30370850","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40567037","id":"PMC_40567037","title":"Plasmodium falciparum acetyltransferase GCN5 acts as a dual regulator of essential glycolytic enzyme phosphoglycerate mutase.","date":"2025","source":"The FEBS journal","url":"https://pubmed.ncbi.nlm.nih.gov/40567037","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase","PfPGM1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42142286","id":"PMC_42142286","title":"Breaking glycolysis: allosteric hotspots for multi-target drug repurposing.","date":"2026","source":"Journal of computer-aided molecular design","url":"https://pubmed.ncbi.nlm.nih.gov/42142286","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoglycerate mutase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7533,"output_tokens":1797,"usd":0.024777,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6810,"output_tokens":2695,"usd":0.050713,"stage2_stop_reason":"end_turn"},"total_usd":0.07549,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"PfPGM1 (PF3D7_1120100) forms a tetramer that is critical for optimal enzymatic activity in vivo; single point mutation W68A abolishes tetramerization and drastically reduces catalytic activity in vitro, while mutation of the conserved residue K100 also leads to drastic reduction in enzymatic activity. Conditional knockdown demonstrated PfPGM1 is essential for intraerythrocytic parasite survival. Ectopic expression of wild-type PfPGM1 enhanced parasite growth, whereas the monomeric (W68) mutant form failed to provide growth advantage.\",\n      \"method\": \"Site-directed mutagenesis, in vitro enzymatic assay, conditional knockdown (loss-of-function), ectopic overexpression with parasite growth readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro mutagenesis + enzymatic assay combined with in vivo conditional knockdown and growth complementation, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"35150741\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PfPGM1 (PF3D7_1120100) is post-translationally regulated by lysine acetylation: the catalytic residue K100 is acetylated by the essential histone acetyltransferase PfGCN5. Acetylation modulates PfPGM1 protein stability rather than directly altering catalytic activity (increasing the protein pool). Additionally, PfGCN5 occupies the PfPGM1 promoter in a stage-specific manner, and knockdown of PfGCN5 reduces PfPGM1 transcript levels, revealing dual regulation (post-translational protein stability and transcriptional control) of PfPGM1 by PfGCN5.\",\n      \"method\": \"Knockdown of PfGCN5 + cycloheximide chase (protein stability assay), ChIP (PfGCN5 promoter occupancy), RT-qPCR (transcript level), in vitro acetyltransferase assay, site-directed mutagenesis (K100)\",\n      \"journal\": \"The FEBS journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — multiple orthogonal methods (ChIP, cycloheximide chase, in vitro acetyltransferase assay, mutagenesis) in a single focused study on PfPGM1\",\n      \"pmids\": [\"40567037\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Phosphoglycerate mutase (PfPGM1/PF3D7_1120100) was identified as a target of protein S-glutathionylation in P. falciparum using enzymatic deglutathionylation, biotin-maleimide affinity purification, and proteomic analysis, indicating it can form a mixed disulfide with glutathione as a redox-sensitive post-translational modification.\",\n      \"method\": \"Enzymatic deglutathionylation, affinity purification (biotin-maleimide), proteomics/mass spectrometry\",\n      \"journal\": \"Antioxidants & redox signaling\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — identified in a proteome-wide screen; no functional follow-up specific to PfPGM1 activity reported in this abstract\",\n      \"pmids\": [\"21595565\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Phosphoglycerate mutase (PF3D7_1120100) was captured as a target of cytosolic thioredoxin 1 (PfTrx-1) in P. falciparum using a cysteine-mutant Trx affinity chromatography approach, identifying it as a substrate in the thioredoxin reduction pathway.\",\n      \"method\": \"Trx-affinity chromatography (cysteine mutant C33S trap), LC-MS/MS\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single affinity pulldown/MS identification; no functional follow-up specific to PfPGM1 reported in this abstract\",\n      \"pmids\": [\"20307687\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Structural and enzymatic comparison established that PfPGM1 (PF3D7_1120100) and PfPGM2 (a paralog) have distinct catalytic conformations; PfPGM1 was used as a reference for sequence/structural comparison, while the characterized PfPGM2 acts primarily as a phosphatase with only residual mutase activity. The two P. falciparum PGMase-family proteins thus have functionally divergent enzymatic activities.\",\n      \"method\": \"Crystal structure determination (of PfPGM2), sequence and structural comparison with PfPGM1, in vitro enzymatic activity assay\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — structural and enzymatic work was performed on PfPGM2 and Cryptosporidium PGM; PfPGM1 was used only for comparative sequence/structural analysis without direct enzymatic characterization of PfPGM1 itself\",\n      \"pmids\": [\"21689687\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfPGM1 (PF3D7_1120100) is an essential glycolytic phosphoglycerate mutase in P. falciparum that functions as a tetramer—tetramerization via residue W68 and catalytic activity via residue K100 are both required for optimal enzymatic function and parasite growth; K100 is acetylated by the acetyltransferase PfGCN5, which modulates PfPGM1 protein stability, while PfGCN5 also transcriptionally controls PfPGM1 expression through stage-specific promoter occupancy, and PfPGM1 can additionally be S-glutathionylated and is a substrate of thioredoxin 1 as part of broader redox regulation in the parasite.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PGM1 (PF3D7_1120100) is an essential phosphoglycerate mutase required for intraerythrocytic survival of Plasmodium falciparum [#0]. It functions as a tetramer: the residue W68 mediates oligomerization, and its mutation to alanine abolishes tetramer formation and drastically reduces catalytic activity in vitro, while the conserved residue K100 is likewise required for enzymatic activity [#0]. Consistent with an essential metabolic role, conditional knockdown impairs parasite growth and ectopic wild-type expression enhances growth, whereas the monomeric W68 mutant confers no growth advantage [#0]. PGM1 is subject to dual control by the acetyltransferase PfGCN5: PfGCN5 acetylates the catalytic K100 residue to increase PGM1 protein stability and pool size rather than to directly alter catalytic rate, and PfGCN5 also occupies the PGM1 promoter in a stage-specific manner such that its knockdown lowers PGM1 transcript levels [#1]. Beyond these established regulatory and structural features, PGM1 has been captured in redox-proteomic screens as a target of S-glutathionylation and as a substrate of cytosolic thioredoxin 1, though no PGM1-specific functional consequence of these modifications has been characterized in the available corpus [#2, #3].\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"To place PGM1 within the parasite's redox network, it was asked whether the enzyme is a substrate of the thioredoxin reduction pathway.\",\n      \"evidence\": \"Trx-affinity chromatography using a cysteine-mutant (C33S) trap with LC-MS/MS identification\",\n      \"pmids\": [\"20307687\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single affinity pulldown/MS identification with no functional follow-up on PGM1 activity\",\n        \"Which cysteine residues are targeted is not defined\",\n        \"The physiological consequence of thioredoxin reduction of PGM1 is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Redox-proteomic screening asked whether PGM1 undergoes reversible thiol modification, testing whether it can form a mixed disulfide with glutathione.\",\n      \"evidence\": \"Enzymatic deglutathionylation with biotin-maleimide affinity purification and proteomic mass spectrometry\",\n      \"pmids\": [\"21595565\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proteome-wide identification without PGM1-specific functional validation\",\n        \"Effect of S-glutathionylation on catalytic activity or tetramerization not tested\",\n        \"Modified residues not mapped\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"To determine whether the two P. falciparum PGMase-family proteins are functionally redundant, PGM1 was compared structurally and enzymatically against its paralog PfPGM2.\",\n      \"evidence\": \"Crystal structure of PfPGM2, sequence/structural comparison with PGM1, and in vitro enzymatic assays\",\n      \"pmids\": [\"21689687\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Direct enzymatic characterization was performed on PfPGM2, not PGM1; PGM1 served only as a comparative reference\",\n        \"No structure of PGM1 itself was determined\",\n        \"The distinct catalytic conformation of PGM1 is inferred, not experimentally solved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The central question of PGM1's essentiality and the structural basis of its activity was resolved by linking tetramerization and specific catalytic residues to enzyme function and parasite growth.\",\n      \"evidence\": \"Site-directed mutagenesis (W68A, K100) with in vitro enzymatic assays, conditional knockdown, and ectopic overexpression growth complementation\",\n      \"pmids\": [\"35150741\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structure of the PGM1 tetramer not solved\",\n        \"Whether K100 contributes to catalysis directly or to substrate binding is not resolved\",\n        \"Metabolic flux consequences of knockdown not quantified\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"How PGM1 abundance is controlled was addressed by identifying PfGCN5 as a dual regulator acting at both the protein-stability and transcriptional levels.\",\n      \"evidence\": \"PfGCN5 knockdown with cycloheximide chase, ChIP for promoter occupancy, RT-qPCR, in vitro acetyltransferase assay, and K100 mutagenesis\",\n      \"pmids\": [\"40567037\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Stoichiometry and dynamics of K100 acetylation in vivo not quantified\",\n        \"The deacetylase counteracting PfGCN5 on PGM1 is unidentified\",\n        \"How acetylation at the catalytic K100 stabilizes protein without altering activity is mechanistically unexplained\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether the redox modifications (S-glutathionylation, thioredoxin reduction) integrate with acetylation and tetramerization to coordinately regulate PGM1 function during the parasite life cycle.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional link established between redox modifications and PGM1 catalytic output\",\n        \"No structural model of the PGM1 tetramer\",\n        \"Cross-talk between transcriptional, acetylation, and redox control of PGM1 not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004619\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006096\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"PGM1 homotetramer (tetramerization dependent on residue W68)\"\n    ],\n    \"partners\": [\n      \"PfGCN5 (histone acetyltransferase; acetylates PGM1 K100 and controls PGM1 transcription)\",\n      \"Cytosolic thioredoxin 1 (PfTrx-1; PGM1 is a substrate)\"\n    ],\n    \"other_free_text\": [\n      \"Essential for intraerythrocytic P. falciparum survival (conditional knockdown loss-of-function).\",\n      \"Catalytic residue K100 required for activity and is the site of PfGCN5-mediated acetylation, which increases protein stability rather than catalytic rate.\",\n      \"Identified as a target of protein S-glutathionylation in redox proteomics.\",\n      \"Paralog PfPGM2 has divergent enzymatic activity (primarily phosphatase); PGM1 served as comparative reference in that structural study.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1120100","name":null,"product":"phosphoglycerate mutase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0928100","name":null,"product":"phosphoglycerate mutase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0917800","name":null,"product":"phosphoglycerate mutase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PGM1","evaluation":null}