Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family.
Acyl carrier protein (ACP) is a universal and highly conserved carrier of acyl intermediates during fatty acid synthesis. In yeast and mammals, ACP exists as a separate domain within a large multifunctional fatty acid synthase polyprotein (type I FAS), whereas it is a small monomeric protein in bacteria and plastids (type II FAS). Bacterial ACPs are also acyl donors for synthesis of a variety of products, including endotoxin and acylated homoserine lactones involved in quorum sensing; the distinct and essential nature of these processes in growth and pathogenesis make ACP-dependent enzymes attractive antimicrobial drug targets. Additionally, ACP homologues are key components in the production of secondary metabolites such as polyketides and nonribosomal peptides. Many ACPs exhibit characteristic structural features of natively unfolded proteins in vitro, with a dynamic and flexible conformation dominated by 3 parallel alpha helices that enclose the thioester-linked acyl group attached to a phosphopantetheine prosthetic group. ACP conformation may also be influenced by divalent cations and interaction with partner enzymes through its "recognition" helix II, properties that are key to its ability to alternately sequester acyl groups and deliver them to the active sites of ACP-dependent enzymes. This review highlights recent progress in defining how the structural features of ACP are related to its multiple carrier roles in fatty acid metabolism.
Atlantic Research Centre, Departments of Pediatrics and Biochemistry & Molecular Biology, Dalhousie University, 5849 University Avenue, Halifax, Nova Scotia, Canada. david.byers@dal.ca
David M
DM
Byers
Huansheng
H
Gong
D000213:Acyl Carrier Protein / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D064429:Fatty Acid Synthases / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D013329:Structure-Activity Relationship
D000213:Acyl Carrier Protein; D005227:Fatty Acids; D064429:Fatty Acid Synthases