The chain-flipping mechanism of ACP (acyl carrier protein)-dependent enzymes appears universal.
ACPs (acyl carrier proteins) play essential roles in the synthesis of fatty acids, polyketides and non-ribosomal polypeptides. ACP function requires the modification of the protein by attachment of 4'-phosphopantetheine to a conserved serine residue. The phosphopantetheine thiol acts to tether the starting materials and intermediates as their thioesters. ACPs are small highly soluble proteins composed of four α-helices. The helices form a bundle that acts as a hydrophobic sleeve that sequesters the acyl chains and activated thioesters from solvent. However, in the synthesis of fatty acids and complex lipids the enzymes of the pathway must access the thioester and the proximal carbon atoms in order to perform the needed chemistry. How such access is provided without exposure of the acyl chains to solvent has been a longstanding question due to the lack of acyl-ACP-enzyme complexes, a situation generally attributed to the brevity of the interactions of acyl-ACPs with their cognate enzymes. As discussed in the present review the access question has now been answered by four recent crystal structures, each of which shows that the entire acyl chain plus the 4'-phosphopantetheine prosthetic group partitions from the ACP hydrophobic sleeve into a hydrophobic pocket or groove of the enzyme protein, a process termed chain flipping.
*Departments of Microbiology and Biochemistry University of Illinois, Urbana, IL 61801, U.S.A.
John E
JE
Cronan
D000213:Acyl Carrier Protein / Q000737:chemistry / Q000378:metabolism*; D000217:Acyltransferases / Q000378:metabolism; D003460:Crystallization; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000378:metabolism; D006836:Hydro-Lyases / Q000378:metabolism; D008958:Models, Molecular; D010204:Pantetheine / Q000031:analogs & derivatives* / Q000378:metabolism; D017433:Protein Structure, Secondary
D000213:Acyl Carrier Protein; D029968:Escherichia coli Proteins; D010204:Pantetheine; D000217:Acyltransferases; C050304:acyl-(acyl-carrier-protein)-UDP-N-acetylglucosamine acyltransferase; D006836:Hydro-Lyases; C047118:3-hydroxyacyl-(acyl-carrier-protein) dehydratase; D054889:Fatty Acid Synthase, Type II; C003129:4'-phosphopantetheine