Acyl carrier protein (ACP) is a small acidic protein which is essential for biosynthetic pathways that depend upon acyl group transfer. The overall structure of E. coli ACP consists of four α-helices connected by three loops. Apo-ACP shows only one conformation, while holo-ACP shows two sets of resonances, suggesting that two conformers are in dynamic equilibrium. We found that the overall nature of inherent local structural variations in these conformers is similar to the nature of structural differences in apo and acylated ACPs. Longer acyl-chain leads to movement of the helix III to expand hydrophobic cavity to accommodate the growing acyl chain and stabilizes one conformation. Spin relaxation experiments as well as model-free analysis indicated that longer acyl chains increase the structural rigidity of ACP. Conformational diversities of holo and acyl ACPs from E. faecalis will be discussed, too.
The rise of multidrug-resistant of bacteria requires the development of new antibiotics. β-Ketoacyl acyl carrier protein synthase (KAS) III is a particularly attractive target in the type II fatty acid synthetic pathway, since it is central to the initiation of fatty acid synthesis. We used receptor-oriented pharmacophore-based in silico screening to find the candidates of inhibitors for KAS III from S. aureus, E. coli, and E. faecalis. We discovered potential inhibitors with nanomolar binding affinity for KAS III and with minimal inhibitory concentration values of 1–2 ug/mL against MRSA. NMR studies to investigate the interactions between acyl-ACP and KAS III revealed that negatively charged residues in second helix of acyl-ACP plays important roles on the electrostatic interactions between acyl-ACP and KAS III. Flexibility of ACP is essential for its ability to interact with functionally different enzyme partners in the rapid delivery of acyl chain from one partner to another.