Acetyl-CoA carboxylase from Escherichia coli exhibits a pronounced hysteresis when inhibited by palmitoyl-acyl carrier protein
Acetyl-CoA carboxylase (ACC) in bacteria is composed of three components: biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase. ACC catalyzes the first committed step in fatty acid synthesis: the carboxylation of acetyl-CoA to form malonyl-CoA via a two-step reaction. In the first half-reaction, biotin carboxylase catalyzes the ATP-dependent carboxylation of the vitamin biotin covalently linked to biotin carboxyl carrier protein. In the second half-reaction, the carboxyl group is transferred from biotin to acetyl-CoA by the enzyme carboxyltransferase, to form malonyl-CoA. In most Gram-negative and Gram-positive bacteria, the three components of ACC form a complex that requires communication for catalysis, and is subject to feedback inhibition by acylated-acyl carrier proteins. This study investigated the mechanism of inhibition of palmitoyl-acyl carrier protein (PACP) on ACC. Unexpectedly, ACC was found to exhibit a significant hysteresis, meaning ACC was subject to inhibition by PACP in a time dependent manner. Pull-down assays demonstrated PACP does not prevent formation of the multiprotein complex, while steady-state kinetic analyses showed PACP inhibited ACC activity allosterically. Structure-activity analyses revealed that the pantothenic acid moiety of PACP is responsible for the inhibition of ACC. This study provides the first evidence of the hysteretic nature of ACC.
Publication Source (Journal or Book title)
Archives of biochemistry and biophysics
Evans, A., Ribble, W., Schexnaydre, E., & Waldrop, G. L. (2017). Acetyl-CoA carboxylase from Escherichia coli exhibits a pronounced hysteresis when inhibited by palmitoyl-acyl carrier protein. Archives of biochemistry and biophysics, 636, 100-109. https://doi.org/10.1016/j.abb.2017.10.016