{"id":"1ff8ed98-93cf-5d7e-bcd0-f04a09270dea","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-tnap-m4-not-catalytic","predicate":"has_structural_not_catalytic_role_at_m4_in","statement":"The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"84f95d4a-d8de-5175-8162-a9f25120b81d","mechanism_event_label":"TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.","subject":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"object":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"84f95d4a-d8de-5175-8162-a9f25120b81d","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-enz-tnap-m4-not-catalytic-event","event_type":"biochemical_relationship","label":"TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.","description":"The recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"m1_m2_catalytic_metals","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"bff427ab-35f9-59c2-bb24-fd5953bbaec2","slug":"magnesium-ion","display_name":"Mg2+","entity_type_key":"ion"},"role":"m3_activation_metal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"3148c377-9b4c-56ca-bc36-081bf1905d57","slug":"alpl","display_name":"Tissue-nonspecific alkaline phosphatase ALPL / TNAP","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"true","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified protein; cell-free assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d1db5bc5-ba8d-508b-8281-982b853a4142","evidence_kind":"source_excerpt","locator":"Lines 820-831","start_line":820,"end_line":831,"excerpt":"### zinc-enz-tnap-m4-not-catalytic\nThe recombinant TNAP mutant study attributed effects of disrupting calcium site M4 to protein structure rather than direct catalysis by M4-bound calcium.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: TNAP metal sites do different jobs: its peripheral calcium site was interpreted as structural.\norganism: Homo sapiens\ntissue_or_cell_type: Purified protein; cell-free assay\nexperimental_model: Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution\nlimitations: This record states the authors’ mechanistic interpretation; existing M3 calcium substitution and Mg/Zn reconstitution claims remain unchanged. It does not imply dietary calcium is a zinc substitute.\nexposure: Recombinant TNAP M4-site mutants and metal-dependent activity comparisons at pH 7.4 and 9.8.\ncross_nutrient: true\n[zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","model_system":"Recombinant human TNAP and M4 mutants; cell-free enzyme activity and metal reconstitution","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-enz-tnap-metals2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase. (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}