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{
"metadata": {
"accession": "PS52019",
"entry_id": null,
"type": "domain",
"go_terms": null,
"source_database": "profile",
"member_databases": null,
"integrated": "IPR049900",
"hierarchy": null,
"name": {
"name": "Polyketide and metazoan fatty acid synthase dehydratase (PKS/mFAS DH) domain profile",
"short": "PKS_MFAS_DH"
},
"description": [
{
"text": "<p>The fundamental polymers of biology-proteins, DNA, and RNA-are products of\nrepetitive condensation of simple amino acid or nucleotide building blocks and\nare comparatively easy to assemble. However, other biomolecules require\nadditional reactions beyond condensation of building blocks. Examples are the\nfatty acids and the polyketide and nonribosomal peptide secondary metabolites.\nThese molecules are produced by complex enzyme assembly lines that include\nmultiple catalytic domains. Modular polyketide synthases (PKSs) systems are\nthought to share a common ancestor with metazoan fatty acid synthases (mFAS).\nBoth have multifunctional polypeptide chains with catalytic domains for\nelongation and modification of intermediate products, which are covalently\nattached to an acyl carrier protein (ACP) domain via a thioester linkage. In\nthe mFAS and modular PKS pathways, intermediate compounds are extended by the\naction of two elongation domains: the acyltransferase (AT) and ketosynthase\n(KS). The beta-keto product of the elongation reactions may be altered by the\nsequential actions of ketoreductase (KR), dehydratase (DH), and enoylreductase\n(ER) modifying domains, which form a hydroxyl group, double bond and single\nbond, respectively. Although fatty acids are synthesized in an iterative\nfashion, with the intermediate chain extended and modified within the same\npolypeptide, modular PKS systems operate in an assembly-line fashion, in which\nintermediates are passed to successive modules in a megacomplex. Dehydratase\ndomains catalyze formation of an alpha,beta-double bond in the nascent\npolyketide intermediate. The mFAS and PKS dehydratase domains are evident\nproducts of gene duplication and fusion, and share a common ancestor with the\nbacterial FAS DH enzymes (FabA and FabZ) [[cite:PUB00153277]][[cite:PUB00055224]][[cite:PUB00153278]]. The product template (PT)\ndomains are PKS/mFAS DH domains that act as an aldol cyclase to control the\nregiospecific aldol cyclization of the extremely reactive poly-beta-ketone\nintermediate assembled by an iterative type I polyketide synthases (PKSs) [[cite:PUB00153279]].\n\nThe PKS/mFAS DH domain comprises two repeats of the hotdog fold. The ~125-residue N-terminal hotdog is slightly shorter than the\n~140-residue C-terminal hotdog. The double-hotdog fold forms a continuous\nantiparallel beta sheet in which the beta strands curve around the \"hotdog\"\nhelices (alphaHD1 from the N-terminal and alphaHD2 from the C-terminal hotdog\nfolds). The double-hotdog core is topped by a cap motif comprising a 3(10)\nhelix, a four-stranded beta sheet, and a single alpha-helix, and additionally,\na short C-terminal 3(10) helix can be considered part of the cap. The DH\nactive site is a His-Asp \"catalytic dyad\", with the histidine from the N-\nterminal hotdog and the aspartate from the C-terminal hotdog [[cite:PUB00055224]][[cite:PUB00153279]].\n\nThe profile we developed covers the entire PKS/mFAS DH domain.</p>",
"llm": false,
"checked": false,
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}
],
"wikipedia": null,
"literature": {
"PUB00153277": {
"PMID": 18772425,
"ISBN": null,
"volume": "321",
"issue": "5894",
"year": 2008,
"title": "An enzyme assembly line",
"URL": null,
"raw_pages": "1304-5",
"medline_journal": "Science",
"ISO_journal": "Science",
"authors": [
"Smith JL",
"Sherman DH."
],
"DOI_URL": "https://doi.org/10.1126/science.1163785"
},
"PUB00153279": {
"PMID": 35618872,
"ISBN": null,
"volume": "5",
"issue": "1",
"year": 2022,
"title": "The Streptomyces viridochromogenes product template domain represents an evolutionary intermediate between dehydratase and aldol cyclase of type I polyketide synthases.",
"URL": null,
"raw_pages": "508",
"medline_journal": "Commun Biol",
"ISO_journal": "Commun Biol",
"authors": [
"Feng Y",
"Yang X",
"Ji H",
"Deng Z",
"Lin S",
"Zheng J."
],
"DOI_URL": "https://doi.org/10.1038/s42003-022-03477-8"
},
"PUB00055224": {
"PMID": 20152156,
"ISBN": null,
"volume": "18",
"issue": "1",
"year": 2010,
"title": "Crystal structures of dehydratase domains from the curacin polyketide biosynthetic pathway.",
"URL": null,
"raw_pages": "94-105",
"medline_journal": "Structure",
"ISO_journal": "Structure",
"authors": [
"Akey DL",
"Razelun JR",
"Tehranisa J",
"Sherman DH",
"Gerwick WH",
"Smith JL."
],
"DOI_URL": "http://dx.doi.org/10.1016/j.str.2009.10.018"
},
"PUB00153278": {
"PMID": 30137093,
"ISBN": null,
"volume": "35",
"issue": "10",
"year": 2018,
"title": "The architectures of iterative type I PKS and FAS.",
"URL": null,
"raw_pages": "1046-1069",
"medline_journal": "Nat Prod Rep",
"ISO_journal": "Nat Prod Rep",
"authors": [
"Herbst DA",
"Townsend CA",
"Maier T."
],
"DOI_URL": "https://doi.org/10.1039/c8np00039e"
}
},
"set_info": null,
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"subfamilies": 0,
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"interactions": 0,
"matches": 60143,
"pathways": 0,
"proteins": 52442,
"proteomes": 6429,
"sets": 0,
"structural_models": {
"alphafold": 3662,
"bfvd": 0
},
"structures": 84,
"taxa": 14153
},
"entry_annotations": {},
"cross_references": {},
"is_llm": false,
"is_reviewed_llm": false,
"is_updated_llm": false,
"representative_structure": {
"accession": "8zev",
"name": "Crystal structure of the dehydratase domain of human fatty acid synthase"
}
}
}
