2AQ9

Structure of E. coli LpxA with a bound peptide that is competitive with acyl-ACP

2AQ9 の概要

• エントリーDOI: 10.2210/pdb2aq9/pdb
• 関連するPDBエントリー: 1LXA
• 分子名称: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase, peptide inhibitor, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: lpxa, peptide inhibitor, acyl acp, acp, udp-glcnac, lipid a, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0A722
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32003.74

構造登録者

Williams, A.H.,Immormino, R.M.,Gewirth, D.T.,Raetz, C.R. (登録日: 2005-08-17, 公開日: 2006-06-27, 最終更新日: 2023-08-23)

主引用文献

Williams, A.H.,Immormino, R.M.,Gewirth, D.T.,Raetz, C.R.
Structure of UDP-N-acetylglucosamine acyltransferase with a bound antibacterial pentadecapeptide.
Proc.Natl.Acad.Sci.Usa, 103:10877-10882, 2006

PubMed Abstract: UDP-GlcNAc acyltransferase (LpxA) catalyzes the first step of lipid A biosynthesis, the transfer of the R-3-hydroxyacyl chain from R-3-hydroxyacyl acyl carrier protein (ACP) to the glucosamine 3-OH group of UDP-GlcNAc. LpxA is essential for the growth of Escherichia coli and related Gram-negative bacteria. The crystal structure of the E. coli LpxA homotrimer, determined previously at 2.6 A in the absence of substrates or inhibitors, revealed that LpxA contains an unusual, left-handed parallel beta-helix fold. We now present the crystal structure at 1.8 A resolution of E. coli LpxA in a complex with a pentadecapeptide, peptide 920. Three peptides, each of which adopts a beta-hairpin conformation, are bound per LpxA trimer. The peptides are located at the interfaces of adjacent subunits in the vicinity of the three active sites. Each peptide interacts with residues from both adjacent subunits. Peptide 920 is a potent inhibitor of E. coli LpxA (Ki = 50 nM). It is competitive with respect to acyl-ACP but not UDP-GlcNAc. The compact beta-turn structure of peptide 920 bound to LpxA may open previously uncharacterized approaches to the rational design of LpxA inhibitors with antibiotic activity.

PubMed: 16835299
DOI: 10.1073/pnas.0604465103

実験手法

X-RAY DIFFRACTION (1.8 Å)