4MDT

Structure of LpxC bound to the reaction product UDP-(3-O-(R-3-hydroxymyristoyl))-glucosamine

4MDT の概要

• エントリーDOI: 10.2210/pdb4mdt/pdb
• 分子名称: UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, ZINC ION, uridine-5'-diphosphate-3-O-(R-3-hydroxymyristoyl)-glucosamine, ... (5 entities in total)
• 機能のキーワード: deacetylase, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 139727.43

構造登録者

Clayton, G.M.,Klein, D.J.,Rickert, K.W.,Patel, S.B.,Kornienko, M.,Zugay-Murphy, J.,Reid, J.C.,Tummala, S.,Sharma, S.,Singh, S.B.,Miesel, L.,Lumb, K.J.,Soisson, S.M. (登録日: 2013-08-23, 公開日: 2013-10-16, 最終更新日: 2023-09-20)

主引用文献

Clayton, G.M.,Klein, D.J.,Rickert, K.W.,Patel, S.B.,Kornienko, M.,Zugay-Murphy, J.,Reid, J.C.,Tummala, S.,Sharma, S.,Singh, S.B.,Miesel, L.,Lumb, K.J.,Soisson, S.M.
Structure of the Bacterial Deacetylase LpxC Bound to the Nucleotide Reaction Product Reveals Mechanisms of Oxyanion Stabilization and Proton Transfer.
J.Biol.Chem., 288:34073-34080, 2013

PubMed Abstract: The emergence of antibiotic-resistant strains of pathogenic bacteria is an increasing threat to global health that underscores an urgent need for an expanded antibacterial armamentarium. Gram-negative bacteria, such as Escherichia coli, have become increasingly important clinical pathogens with limited treatment options. This is due in part to their lipopolysaccharide (LPS) outer membrane components, which dually serve as endotoxins while also protecting Gram-negative bacteria from antibiotic entry. The LpxC enzyme catalyzes the committed step of LPS biosynthesis, making LpxC a promising target for new antibacterials. Here, we present the first structure of an LpxC enzyme in complex with the deacetylation reaction product, UDP-(3-O-(R-3-hydroxymyristoyl))-glucosamine. These studies provide valuable insight into recognition of substrates and products by LpxC and a platform for structure-guided drug discovery of broad spectrum Gram-negative antibiotics.

PubMed: 24108127
DOI: 10.1074/jbc.M113.513028

実験手法

X-RAY DIFFRACTION (2.59 Å)