3P3C

Crystal Structure of the Aquifex aeolicus LpxC/LPC-009 complex

3P3C の概要

• エントリーDOI: 10.2210/pdb3p3c/pdb
• 関連するPDBエントリー: 2JT2 3P3E 3P3G
• 分子名称: UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, ZINC ION, N-[(1S,2R)-2-hydroxy-1-(hydroxycarbamoyl)propyl]-4-(4-phenylbuta-1,3-diyn-1-yl)benzamide, ... (5 entities in total)
• 機能のキーワード: lipid a biosynthesis, lipid a synthesis, lpxc, baab sandwich, hydrolase, deacetylation, antibiotic, acyl udp-glcnac, hydroxamate, lpc-009
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31844.57

構造登録者

Lee, C.-J.,Zhou, P. (登録日: 2010-10-04, 公開日: 2011-01-05, 最終更新日: 2024-02-21)

主引用文献

Lee, C.J.,Liang, X.,Chen, X.,Zeng, D.,Joo, S.H.,Chung, H.S.,Barb, A.W.,Swanson, S.M.,Nicholas, R.A.,Li, Y.,Toone, E.J.,Raetz, C.R.,Zhou, P.
Species-specific and inhibitor-dependent conformations of LpxC: implications for antibiotic design.
Chem.Biol., 18:38-47, 2011

PubMed Abstract: LpxC is an essential enzyme in the lipid A biosynthetic pathway in gram-negative bacteria. Several promising antimicrobial lead compounds targeting LpxC have been reported, though they typically display a large variation in potency against different gram-negative pathogens. We report that inhibitors with a diacetylene scaffold effectively overcome the resistance caused by sequence variation in the LpxC substrate-binding passage. Compound binding is captured in complex with representative LpxC orthologs, and structural analysis reveals large conformational differences that mostly reflect inherent molecular features of distinct LpxC orthologs, whereas ligand-induced structural adaptations occur at a smaller scale. These observations highlight the need for a molecular understanding of inherent structural features and conformational plasticity of LpxC enzymes for optimizing LpxC inhibitors as broad-spectrum antibiotics against gram-negative infections.

PubMed: 21167751
DOI: 10.1016/j.chembiol.2010.11.011

実験手法

X-RAY DIFFRACTION (1.25 Å)