4MDT

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

Summary for 4MDT

• Entry DOI: 10.2210/pdb4mdt/pdb
• Descriptor: UDP-3-O-[3-hydroxymyristoyl] N-acetylglucosamine deacetylase, ZINC ION, uridine-5'-diphosphate-3-O-(R-3-hydroxymyristoyl)-glucosamine, ... (5 entities in total)
• Functional Keywords: deacetylase, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 4
• Total formula weight: 139727.43

Authors

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. (deposition date: 2013-08-23, release date: 2013-10-16, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.59 Å)