{"corpus_id":37223161,"paper_sha":"b802c702219025e5431fd847686927c63e312aca","doi":"10.1016/s0021-9258(17)43808-7","arxiv_id":null,"pmid":6654914,"pmcid":null,"mag_id":1528395898,"dblp_id":null,"acl_id":null,"title":"The architecture of the animal fatty acid synthetase complex. IV. Mapping of active centers and model for the mechanism of action.","year":1983,"publication_date":"1983-12-25","venue":"Journal of Biological Chemistry","journal":{"name":"The Journal of biological chemistry","pages":"\n          15312-22\n        ","volume":"258 24"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't","Research Support, U.S. Gov't, P.H.S."],"s2_fields_of_study":["Biology","Medicine","Chemistry"],"reference_count":0,"citation_count":66,"influential_citation_count":0,"is_open_access":false,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Acyl Carrier Protein","mj":false,"qs":[{"q":"analysis","mj":false,"ui":"Q000032"}],"ui":"D000213"},{"d":"Amino Acid Sequence","mj":false,"ui":"D000595"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Binding Sites","mj":false,"ui":"D001665"},{"d":"Chickens","mj":false,"ui":"D002645"},{"d":"Fatty Acid Synthases","mj":false,"qs":[{"q":"analysis","mj":true,"ui":"Q000032"}],"ui":"D064429"},{"d":"Kinetics","mj":false,"ui":"D007700"},{"d":"Liver","mj":false,"qs":[{"q":"enzymology","mj":false,"ui":"Q000201"}],"ui":"D008099"},{"d":"Macromolecular Substances","mj":false,"ui":"D046911"},{"d":"Molecular Weight","mj":false,"ui":"D008970"},{"d":"NADP","mj":false,"qs":[{"q":"pharmacology","mj":false,"ui":"Q000494"}],"ui":"D009249"}],"chemicals":[{"n":"Acyl Carrier Protein","ui":"D000213","reg":"0"},{"n":"Macromolecular Substances","ui":"D046911","reg":"0"},{"n":"NADP","ui":"D009249","reg":"53-59-8"},{"n":"Fatty Acid Synthases","ui":"D064429","reg":"EC 2.3.1.85"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":null,"s2_open_access_landing_url":null,"s2_open_access_license":null,"s2_open_access_status":null,"pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"The fatty acid synthetase of animal tissue consists of two subunits, each containing seven catalytic centers and an acyl carrier site. Proteolytic cleavage patterns indicate that the subunit is arranged into three major domains, I, II, and III. Domain I contains the NH2-terminal end of the polypeptide and the catalytic sites of beta-ketoacyl synthetase (condensing enzyme) and the acetyl-and malonyl-transacylases. This domain, therefore, functions as a site for acetyl and malonyl substrate entry into the process of fatty acid synthesis and acts in part as the site of carbon-carbon condensation, resulting in chain elongation. Domain II is the medial domain and contains the beta-ketoacyl and enoyl reductases, probably the dehydratase, and the 4'-phosphopantetheine prosthetic group of the acyl carrier protein site. Domain II, therefore, is designated as the reduction domain where the keto carbon is reduced to methylene carbon by sequential processes of reduction, dehydration, and reduction again. Throughout these processes, the acyl group is attached to the pantetheine-SH of the acyl carrier protein. The latter site is distal to the cysteine-SH of the beta-ketoacyl synthetase, constitutes the 15000-dalton polypeptide at the COOH-terminal end of Domain II, and connects to Domain III. When the growing chain reaches C16 carbon length, the fatty acyl group is released by the thioesterase activity, which is contained in Domain III. A functional model is proposed based on the aforementioned results and the recent evidence that the synthetase subunits are arranged in a head-to-tail fashion, such that the pantetheine-SH of the acyl carrier protein of one subunit and the cysteine-SH of the beta-ketoacyl synthetase of the second subunit are juxtaposed. In this model, a palmitate synthesizing site contains Domain I of one subunit and Domains II and III of the second subunit. Therefore, even though each subunit contains all of the partial activities of the reaction sequence, the actual palmitate synthesizing unit consists of one-half of a subunit interacting with the complementary half of the other subunit.","claims":[{"public_id":"cl_3f368100effa90e5d4e2745894357e04","status":"active","text":"A head-to-tail subunit arrangement is proposed in which the palmitate-synthesizing site is formed by Domain I of one subunit together with Domains II and III of the दूसरे subunit, so the functional palmitate-synthesizing unit spans complementary halves of two interacting subunits.","confidence":0.93,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_3f368100effa90e5d4e2745894357e04"},{"public_id":"cl_14bbd15b01ad65bb99ea5e67ca0a2e16","status":"active","text":"Domain I contains the beta-ketoacyl synthetase, acetyl-transacylase, and malonyl-transacylase catalytic sites and functions in acetyl and malonyl substrate entry and carbon-carbon condensation during chain elongation.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_14bbd15b01ad65bb99ea5e67ca0a2e16"},{"public_id":"cl_9c98585de5772b672292a27e049d72e2","status":"active","text":"Domain II contains the beta-ketoacyl reductase, enoyl reductase, probably the dehydratase, and the 4'-phosphopantetheine prosthetic group, and serves as the reduction domain in which the keto carbon is converted to methylene carbon through sequential reduction, dehydration, and reduction.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_9c98585de5772b672292a27e049d72e2"},{"public_id":"cl_0052dbe6d9f96a49c0e77b6e53eabb3c","status":"active","text":"Proteolytic cleavage patterns support a three-domain organization of the animal fatty acid synthetase subunit: Domain I, Domain II, and Domain III.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_0052dbe6d9f96a49c0e77b6e53eabb3c"},{"public_id":"cl_3f78f044ff8ed0fba1ace6e56228480e","status":"active","text":"The growing acyl chain remains attached to the pantetheine-SH of the acyl carrier protein, and fatty acyl groups are released at C16 by thioesterase activity in Domain III.","confidence":0.94,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_3f78f044ff8ed0fba1ace6e56228480e"}],"concepts":[{"public_id":"co_0f8ef318987ec5b8d60807e76a685384","status":"active","name":"thioesterase activity","description":"An enzymatic activity that releases fatty acyl chains from the synthetase by hydrolyzing thioester bonds.","types":["enzyme activity"],"aliases":[],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/concepts/co_0f8ef318987ec5b8d60807e76a685384"},{"public_id":"co_2a2d20c8c6c73715db1d3d69f530cde1","status":"active","name":"acyl carrier protein site","description":"The site that holds the growing acyl group through attachment to its pantetheine-SH group.","types":["binding site"],"aliases":["ACP site"],"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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