title: Catalytic residues are shared between two pseudosubunits of the dehydratase domain of the animal fatty acid synthase.
abstract: Expression, characterization, and mutagenesis of a series of N-terminal fragments of an animal fatty acid synthase, containing the beta-ketoacyl synthase, acyl transferase, and dehydratase domains, demonstrate that the dehydratase domain consists of two pseudosubunits, derived from contiguous regions of the same polypeptide, in which a single active site is formed by the cooperation of the catalytic histidine 878 residue of the first pseudosubunit with aspartate 1032 of the second pseudosubunit. Mutagenesis and modeling studies revealed an essential role for glutamine 1036 in anchoring the position of the catalytic aspartate. These findings establish that sequence elements previously assigned to a central structural core region of the type I fatty acid synthases and some modular polyketide synthase counterparts play an essential catalytic role as part of the dehydratase domain.
authors: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609-1673, USA.
authors: Saloni
authors: S
authors: Pasta
authors: Andrzej
authors: A
authors: Witkowski
authors: Anil K
authors: AK
authors: Joshi
authors: Stuart
authors: S
authors: Smith
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000737:chemistry; D000217:Acyltransferases / Q000737:chemistry; D019943:Amino Acid Substitution; D000818:Animals; D002384:Catalysis; D020134:Catalytic Domain; D019281:Dimerization; D054890:Fatty Acid Synthase, Type I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006836:Hydro-Lyases / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D008970:Molecular Weight; D017434:Protein Structure, Tertiary; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D000217:Acyltransferases; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054890:Fatty Acid Synthase, Type I; D006836:Hydro-Lyases