title: The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs.
abstract: While X-ray and NMR structures are now available for most components of the Type II fatty acid synthase (FAS), there are no structures for Type I FAS domains. A region from the mammalian (rat) FAS, including the putative acyl carrier protein (ACP), has been cloned and over-expressed. Here we report multinuclear, multidimensional NMR studies which show that this isolated ACP domain contains four alpha-helices (residues 8-16 [1]; 41-51 [2]; 58-63 [3] and 66-74 [4]) and an overall global fold characteristic of ACPs from both Type II FAS and polyketide synthases (PKSs). The overall length of the structured ACP domain (67 residues) is smaller than the structured regions of the Eschericia coli FAS ACP (75 residues), the actinorhodin PKS ACP (78 residues) and the Bacillus subtilis FAS ACP (76 residues). We further show that the rat FAS ACP is recognised as an efficient substrate by enzymes known to modify Type II ACPs including phosphopantetheinyl and malonyl transferases, but not by the heterologous S. coelicolor minimal polyketide synthase.
authors.affiliation: School of Chemistry, University of Bristol, Cantock's Close, Bristol, UK BS8 1 TS.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Reed
authors.forename: Michael
authors.initials: M
authors.lastname: Schweizer
authors.forename: Anna E
authors.initials: AE
authors.lastname: Szafranska
authors.forename: Chris
authors.initials: C
authors.lastname: Arthur
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Nicholson
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Cox
authors.forename: John
authors.initials: J
authors.lastname: Crosby
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Crump
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Simpson
mesh_terms: D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001407:Bacillus / Q000201:enzymology / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D064429:Fatty Acid Synthases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D020033:Protein Isoforms; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D040681:Structural Homology, Protein
chemical_list: D000213:Acyl Carrier Protein; D009097:Multienzyme Complexes; D020033:Protein Isoforms; D011994:Recombinant Proteins; D000217:Acyltransferases; D064429:Fatty Acid Synthases