4J09

Crystal Structure of LpxA bound to RJPXD33

4J09 の概要

• エントリーDOI: 10.2210/pdb4j09/pdb
• 分子名称: Acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase, Putative metabolite transport protein YjhB, PHOSPHATE ION, ... (6 entities in total)
• 機能のキーワード: acyltransferase, left-handed beta helix, transferase
• 由来する生物種: Escherichia coli; 詳細
• 細胞内の位置: Cytoplasm: P0A722; Cell inner membrane; Multi-pass membrane protein (Potential): P39352
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 29358.11

構造登録者

Jenkins, R.J.,Meagher, J.L.,Stuckey, J.A.,Dotson, G.D. (登録日: 2013-01-30, 公開日: 2014-04-23, 最終更新日: 2024-02-28)

主引用文献

Jenkins, R.J.,Heslip, K.A.,Meagher, J.L.,Stuckey, J.A.,Dotson, G.D.
Structural Basis for the Recognition of Peptide RJPXD33 by Acyltransferases in Lipid A Biosynthesis.
J.Biol.Chem., 289:15527-15535, 2014

PubMed Abstract: UDP-N-acetylglucosamine acyltransferase (LpxA) and UDP-3-O-(acyl)-glucosamine acyltransferase (LpxD) constitute the essential, early acyltransferases of lipid A biosynthesis. Recently, an antimicrobial peptide inhibitor, RJPXD33, was identified with dual affinity for LpxA and LpxD. To gain a fundamental understanding of the molecular basis of inhibitor binding, we determined the crystal structure of LpxA from Escherichia coli in complex with RJPXD33 at 1.9 Å resolutions. Our results suggest that the peptide binds in a unique modality that mimics (R)-β-hydroxyacyl pantetheine binding to LpxA and displays how the peptide binds exclusive of the native substrate, acyl-acyl carrier protein. Acyltransferase binding studies with photo-labile RJPXD33 probes and truncations of RJPXD33 validated the structure and provided fundamental insights for future design of small molecule inhibitors. Overlay of the LpxA-RJPXD33 structure with E. coli LpxD identified a complementary peptide binding pocket within LpxD and serves as a model for further biochemical characterization of RJPXD33 binding to LpxD.

PubMed: 24742680
DOI: 10.1074/jbc.M114.564278

実験手法

X-RAY DIFFRACTION (1.9 Å)