Structure guided design of an antibacterial peptide that targets UDP-N-acetylglucosamine acyltransferase.

ABSTRACT: UDP-N-acetylglucosamine (UDP-GlcNAc) acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of an R-3-hydroxyacyl chain from its acyl carrier protein (ACP) to the 3-OH group of UDP-GlcNAc. Essential in the growth of Gram-negative bacteria, LpxA is a logical target for antibiotics design. A pentadecapeptide (Peptide 920) with high affinity towards LpxA was previously identified in a phage display library. Here we created a small library of systematically designed peptides with the length of four to thirteen amino acids using Peptide 920 as a scaffold. The concentrations of these peptides at which 50% of LpxA is inhibited (IC₅₀) range from 50 nM to >100 μM. We determined the crystal structure of E. coli LpxA in a complex with a potent inhibitor. LpxA

SUBMITTER: Dangkulwanich M 

PROVIDER: S-EPMC6408518 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature