{"id":"3ae04b9b-b377-579d-aa60-73aa8e9fefd8","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-cbs-sam-allostery","predicate":"activates","statement":"SAM binding rearranged the human CBS regulatory domain and relieved autoinhibition, improving access to its catalytic pocket.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"4d2e11dc-8d73-52e9-87cf-8d62e96b5bbf","mechanism_event_label":"A plentiful methyl donor can turn up the sulfur-transfer branch.","subject":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"object":{"id":"4688e32c-d7b6-5fca-9eb2-23307c29ae07","slug":"cbs","display_name":"Human cystathionine beta-synthase / CBS","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"4d2e11dc-8d73-52e9-87cf-8d62e96b5bbf","stable_key":"41a89233-da9a-5b7b-9c18-e19bbadcfe2d:methionine-cbs-sam-allostery-event","event_type":"observed_relationship","label":"A plentiful methyl donor can turn up the sulfur-transfer branch.","description":"SAM binding rearranged the human CBS regulatory domain and relieved autoinhibition, improving access to its catalytic pocket.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"825f2da2-01bc-5874-a3c6-64f5ac867db5","slug":"s-adenosylmethionine","display_name":"S-Adenosyl-L-methionine","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4688e32c-d7b6-5fca-9eb2-23307c29ae07","slug":"cbs","display_name":"Human cystathionine beta-synthase / CBS","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9d39f561-740b-5f67-bba7-8a72ef612a99","slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"5b635b42-bc0d-5c54-aa94-9cf76cd0ed47","slug":"homocysteine","display_name":"Homocysteine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ca899f13-50ad-55e5-ab99-329ae0038c74","slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"6b656ff5-9532-5da4-8eea-8ca163a48649","slug":"pyridoxal-phosphate","display_name":"PLP","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human CBS structural study with SAM-bound activated conformation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Allosteric regulation does not establish in-vivo flux under every nutritional condition.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Methionine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"methionine","display_name":"L-Methionine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A plentiful methyl donor can turn up the sulfur-transfer branch.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0421b6a9-3975-51d4-91ed-e3c6889b6045","evidence_kind":"source_excerpt","locator":"Lines 204-210","start_line":204,"end_line":210,"excerpt":"## methionine-cbs-sam-allostery\nA plentiful methyl donor can turn up the sulfur-transfer branch.\nSAM binding rearranged the human CBS regulatory domain and relieved autoinhibition, improving access to its catalytic pocket.\nModel: Human CBS structural study with SAM-bound activated conformation.\nLimitations: Allosteric regulation does not establish in-vivo flux under every nutritional condition.\nEvidence access: Primary abstract\nStructural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25197074/ · DOI 10.1073/pnas.1414545111","model_system":"Human CBS structural study with SAM-bound activated conformation.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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