3P76

X-ray crystal structure of Aquifex aeolicus LpxC complexed SCH1379777

3P76 の概要

• エントリーDOI: 10.2210/pdb3p76/pdb
• 分子名称: UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, IMIDAZOLE, N-[(1S,2R)-2-hydroxy-1-(hydroxycarbamoyl)propyl]-4-[4-(phenylethynyl)phenyl]piperidine-1-carboxamide, ... (5 entities in total)
• 機能のキーワード: amidohydrolases, amino acid motifs, binding sites, drug design, enzyme inhibitors, escherichia coli proteins, hydrophobicity, lipid a, protein conformation, protein folding, recombinant fusion proteins, structure-activity relationship, hydrolase
• 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: 31610.90

構造登録者

Orth, P. (登録日: 2010-10-12, 公開日: 2011-02-09, 最終更新日: 2023-09-06)

主引用文献

Faruk Mansoor, U.,Vitharana, D.,Reddy, P.A.,Daubaras, D.L.,McNicholas, P.,Orth, P.,Black, T.,Arshad Siddiqui, M.
Design and synthesis of potent Gram-negative specific LpxC inhibitors.
Bioorg.Med.Chem.Lett., 21:1155-1161, 2011

PubMed Abstract: Antibiotic resistant hospital acquired infections are on the rise, creating an urgent need for novel bactericidal drugs. Enzymes involved in lipopolysaccharide (LPS) biosynthesis are attractive antibacterial targets since LPS is the major structural component of the outer membrane of Gram-negative bacteria. Lipid A is an essential hydrophobic anchor of LPS and the first committed step in lipid A biosynthesis is catalyzed by a unique zinc dependent metalloamidase, UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC). LpxC is an attractive Gram-negative only target that has been chemically validated by potent bactericidal hydroxamate inhibitors that work by coordination of the enzyme's catalytic zinc ion. An exploratory chemistry effort focused on expanding the SAR around hydroxamic acid zinc-binding 'warheads' lead to the identification of novel compounds with enzyme potency and antibacterial activity similar to CHIR-090.

PubMed: 21273067
DOI: 10.1016/j.bmcl.2010.12.111

実験手法

X-RAY DIFFRACTION (1.93 Å)