{"gene":"TG_286630","gene_symbol":"AHP1","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2021,"finding":"TgAHP1 is a peroxiredoxin-family protein with cysteine-dependent peroxidase activity; Cys166 was identified as the key catalytic active site, and the enzyme follows a cysteine-dependent redox mechanism.","method":"Active-site mutagenesis (Cys166 mutation) and in vitro/cellular peroxidase activity assay","journal":"Oxidative medicine and cellular longevity","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — active-site mutagenesis with functional assay, but single lab and abstract-level detail only","pmids":["34603593"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"TgAHP1 localises in a punctate staining pattern anterior to the T. gondii nucleus, consistent with a peroxisomal localisation, as established by direct imaging.","method":"Fluorescence microscopy / subcellular localisation imaging","journal":"Oxidative medicine and cellular longevity","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct imaging in fixed parasites, single lab, no functional consequence directly linked to localisation in this paper","pmids":["34603593"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Loss of TgAHP1 (ΔAhp1 strain) renders parasites more sensitive to tert-butyl hydroperoxide (tBOOH) than to H2O2, indicating tBOOH is a preferred substrate; under tBOOH stress, ΔAhp1 parasites accumulate elevated ROS and undergo apoptosis, resulting in reduced invasion, proliferation, and virulence in mice.","method":"Genetic knockout (ΔAhp1), ROS measurement, invasion/proliferation assays, mouse virulence model","journal":"Oxidative medicine and cellular longevity","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with multiple orthogonal phenotypic readouts (ROS, invasion, replication, in vivo), single lab","pmids":["34603593"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"TgAHP1 interacts with TgURM1 (ubiquitin-related modifier 1) specifically under oxidative stress conditions, identified by proximity-based protein labelling (BioID-type) and proteomics, indicating TgAHP1 is a target of urmylation in the antioxidant stress response.","method":"Proximity-based protein labelling (BioID) and mass spectrometry proteomics; interaction validated under oxidative stress","journal":"Microbiology spectrum","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — proximity labelling plus proteomics in two papers (PMID 35323018 and 36142209) from the same lab; interaction is stress-dependent and consistently reported","pmids":["35323018","36142209"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgAHP1 is a peroxisomal, cysteine-dependent peroxidase (active site Cys166) that preferentially reduces alkyl hydroperoxides (tBOOH > H2O2); under oxidative stress it is urmylated via the TgURM1/TgUBA1 conjugation pathway, and its loss causes ROS accumulation, apoptosis, and impaired parasite invasion, replication, and virulence."},"narrative":{"mechanistic_narrative":"TgAHP1 is a peroxiredoxin-family antioxidant enzyme that protects Toxoplasma gondii against oxidative stress by acting as a cysteine-dependent peroxidase, using the active-site Cys166 to reduce hydroperoxides through a thiol-based redox mechanism [PMID:34603593]. It displays substrate preference for alkyl hydroperoxides over H2O2, and its loss sensitizes parasites specifically to tert-butyl hydroperoxide, leading to ROS accumulation, apoptosis, and impaired invasion, proliferation, and virulence in mice [PMID:34603593]. The enzyme localizes in a punctate pattern anterior to the nucleus consistent with peroxisomal targeting [PMID:34603593], and under oxidative stress it is a target of the urmylation pathway, interacting with the ubiquitin-related modifier TgURM1 in a stress-dependent manner [PMID:35323018, PMID:36142209]. Beyond these findings, the structural basis of catalysis and the functional consequence of urmylation on TgAHP1 activity have not been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Establishing that TgAHP1 is an active peroxidase answered whether the protein has intrinsic antioxidant enzymatic function and pinpointed the catalytic residue driving it.","evidence":"Active-site mutagenesis of Cys166 with in vitro and cellular peroxidase activity assays in T. gondii","pmids":["34603593"],"confidence":"Medium","gaps":["No structural model or resolving-cysteine/regeneration partner identified","Abstract-level detail from a single lab","Catalytic cycle and electron donor not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Subcellular imaging addressed where the enzyme acts, placing TgAHP1 in a punctate compartment consistent with peroxisomal localization.","evidence":"Fluorescence microscopy of fixed parasites showing punctate staining anterior to the nucleus","pmids":["34603593"],"confidence":"Medium","gaps":["Peroxisomal identity inferred from pattern, not confirmed by co-localization with a peroxisomal marker","No functional consequence directly tied to localization"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"Genetic knockout defined the physiological substrate preference and the biological importance of TgAHP1, showing alkyl hydroperoxide detoxification is required for parasite fitness and virulence.","evidence":"ΔAhp1 knockout with ROS measurement, invasion/proliferation assays, and mouse virulence model","pmids":["34603593"],"confidence":"Medium","gaps":["Molecular mechanism linking ROS accumulation to apoptosis not defined","Single lab; substrate preference shown phenotypically rather than by enzyme kinetics"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Interaction proteomics connected TgAHP1 to the urmylation pathway, revealing a post-translational modification layer engaged specifically during oxidative stress.","evidence":"Proximity-based labelling (BioID) and mass spectrometry proteomics in T. gondii; TgURM1 interaction validated under oxidative stress","pmids":["35323018","36142209"],"confidence":"Medium","gaps":["Functional consequence of urmylation on TgAHP1 activity, stability, or localization not established","Urmylated residue not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How urmylation modulates TgAHP1 peroxidase activity and how the enzyme is regenerated in its catalytic cycle remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural characterization of the active site","Reducing/regeneration partner unknown","Direct link between urmylation and enzymatic outcome untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGURM1 (UBIQUITIN-RELATED MODIFIER 1; STRESS-DEPENDENT INTERACTION)"],"other_free_text":["Catalytic active site Cys166 drives a cysteine-dependent redox mechanism [#0]","Substrate preference for alkyl hydroperoxides (tBOOH) over H2O2 [#2]","Loss of TgAHP1 causes ROS accumulation, apoptosis, and reduced invasion, proliferation, and virulence [#2]","Urmylation of TgAHP1 occurs specifically under oxidative stress [#3]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"35323018","id":"PMC_35323018","title":"Involvement of Urm1, a Ubiquitin-Like Protein, in the Regulation of Oxidative Stress Response of Toxoplasma gondii.","date":"2022","source":"Microbiology spectrum","url":"https://pubmed.ncbi.nlm.nih.gov/35323018","citation_count":13,"is_preprint":false},{"pmid":"34603593","id":"PMC_34603593","title":"Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii.","date":"2021","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/34603593","citation_count":6,"is_preprint":false},{"pmid":"36142209","id":"PMC_36142209","title":"Uba1: A Potential Ubiquitin-like Activator Protein of Urm1 in Toxoplasma gondii.","date":"2022","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/36142209","citation_count":4,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4032,"output_tokens":1080,"usd":0.014148,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6007,"output_tokens":2243,"usd":0.043055,"stage2_stop_reason":"end_turn"},"total_usd":0.057203,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"TgAHP1 is a peroxiredoxin-family protein with cysteine-dependent peroxidase activity; Cys166 was identified as the key catalytic active site, and the enzyme follows a cysteine-dependent redox mechanism.\",\n      \"method\": \"Active-site mutagenesis (Cys166 mutation) and in vitro/cellular peroxidase activity assay\",\n      \"journal\": \"Oxidative medicine and cellular longevity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — active-site mutagenesis with functional assay, but single lab and abstract-level detail only\",\n      \"pmids\": [\"34603593\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TgAHP1 localises in a punctate staining pattern anterior to the T. gondii nucleus, consistent with a peroxisomal localisation, as established by direct imaging.\",\n      \"method\": \"Fluorescence microscopy / subcellular localisation imaging\",\n      \"journal\": \"Oxidative medicine and cellular longevity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct imaging in fixed parasites, single lab, no functional consequence directly linked to localisation in this paper\",\n      \"pmids\": [\"34603593\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Loss of TgAHP1 (ΔAhp1 strain) renders parasites more sensitive to tert-butyl hydroperoxide (tBOOH) than to H2O2, indicating tBOOH is a preferred substrate; under tBOOH stress, ΔAhp1 parasites accumulate elevated ROS and undergo apoptosis, resulting in reduced invasion, proliferation, and virulence in mice.\",\n      \"method\": \"Genetic knockout (ΔAhp1), ROS measurement, invasion/proliferation assays, mouse virulence model\",\n      \"journal\": \"Oxidative medicine and cellular longevity\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with multiple orthogonal phenotypic readouts (ROS, invasion, replication, in vivo), single lab\",\n      \"pmids\": [\"34603593\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"TgAHP1 interacts with TgURM1 (ubiquitin-related modifier 1) specifically under oxidative stress conditions, identified by proximity-based protein labelling (BioID-type) and proteomics, indicating TgAHP1 is a target of urmylation in the antioxidant stress response.\",\n      \"method\": \"Proximity-based protein labelling (BioID) and mass spectrometry proteomics; interaction validated under oxidative stress\",\n      \"journal\": \"Microbiology spectrum\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — proximity labelling plus proteomics in two papers (PMID 35323018 and 36142209) from the same lab; interaction is stress-dependent and consistently reported\",\n      \"pmids\": [\"35323018\", \"36142209\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgAHP1 is a peroxisomal, cysteine-dependent peroxidase (active site Cys166) that preferentially reduces alkyl hydroperoxides (tBOOH > H2O2); under oxidative stress it is urmylated via the TgURM1/TgUBA1 conjugation pathway, and its loss causes ROS accumulation, apoptosis, and impaired parasite invasion, replication, and virulence.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgAHP1 is a peroxiredoxin-family antioxidant enzyme that protects Toxoplasma gondii against oxidative stress by acting as a cysteine-dependent peroxidase, using the active-site Cys166 to reduce hydroperoxides through a thiol-based redox mechanism [#0]. It displays substrate preference for alkyl hydroperoxides over H2O2, and its loss sensitizes parasites specifically to tert-butyl hydroperoxide, leading to ROS accumulation, apoptosis, and impaired invasion, proliferation, and virulence in mice [#2]. The enzyme localizes in a punctate pattern anterior to the nucleus consistent with peroxisomal targeting [#1], and under oxidative stress it is a target of the urmylation pathway, interacting with the ubiquitin-related modifier TgURM1 in a stress-dependent manner [#3]. Beyond these findings, the structural basis of catalysis and the functional consequence of urmylation on TgAHP1 activity have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Establishing that TgAHP1 is an active peroxidase answered whether the protein has intrinsic antioxidant enzymatic function and pinpointed the catalytic residue driving it.\",\n      \"evidence\": \"Active-site mutagenesis of Cys166 with in vitro and cellular peroxidase activity assays in T. gondii\",\n      \"pmids\": [\"34603593\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model or resolving-cysteine/regeneration partner identified\",\n        \"Abstract-level detail from a single lab\",\n        \"Catalytic cycle and electron donor not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Subcellular imaging addressed where the enzyme acts, placing TgAHP1 in a punctate compartment consistent with peroxisomal localization.\",\n      \"evidence\": \"Fluorescence microscopy of fixed parasites showing punctate staining anterior to the nucleus\",\n      \"pmids\": [\"34603593\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Peroxisomal identity inferred from pattern, not confirmed by co-localization with a peroxisomal marker\",\n        \"No functional consequence directly tied to localization\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Genetic knockout defined the physiological substrate preference and the biological importance of TgAHP1, showing alkyl hydroperoxide detoxification is required for parasite fitness and virulence.\",\n      \"evidence\": \"ΔAhp1 knockout with ROS measurement, invasion/proliferation assays, and mouse virulence model\",\n      \"pmids\": [\"34603593\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism linking ROS accumulation to apoptosis not defined\",\n        \"Single lab; substrate preference shown phenotypically rather than by enzyme kinetics\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Interaction proteomics connected TgAHP1 to the urmylation pathway, revealing a post-translational modification layer engaged specifically during oxidative stress.\",\n      \"evidence\": \"Proximity-based labelling (BioID) and mass spectrometry proteomics in T. gondii; TgURM1 interaction validated under oxidative stress\",\n      \"pmids\": [\"35323018\", \"36142209\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of urmylation on TgAHP1 activity, stability, or localization not established\",\n        \"Urmylated residue not mapped\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How urmylation modulates TgAHP1 peroxidase activity and how the enzyme is regenerated in its catalytic cycle remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural characterization of the active site\",\n        \"Reducing/regeneration partner unknown\",\n        \"Direct link between urmylation and enzymatic outcome untested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051920\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0004601\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006979\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0032447\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TgURM1 (ubiquitin-related modifier 1; stress-dependent interaction)\"\n    ],\n    \"other_free_text\": [\n      \"Catalytic active site Cys166 drives a cysteine-dependent redox mechanism [#0]\",\n      \"Substrate preference for alkyl hydroperoxides (tBOOH) over H2O2 [#2]\",\n      \"Loss of TgAHP1 causes ROS accumulation, apoptosis, and reduced invasion, proliferation, and virulence [#2]\",\n      \"Urmylation of TgAHP1 occurs specifically under oxidative stress [#3]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_286630","name":"AHP1","product":"alkyl hydroperoxide reductase AHP1","uniprot_acc":"A0A125YMB2","chromosome":"TGME49_chrV","start_pos":1751406},{"strain":"GT1","gene_id":"TGGT1_286630","name":null,"product":"redoxin domain-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrV","start_pos":1606591},{"strain":"RH88","gene_id":"TGRH88_025560","name":null,"product":"redoxin domain-containing protein","uniprot_acc":null,"chromosome":"CM023086","start_pos":1784678},{"strain":"VEG","gene_id":"TGVEG_286630","name":null,"product":"redoxin domain-containing protein","uniprot_acc":"A0A125YPC3","chromosome":"TGVEG_chrV","start_pos":1708283}]}