4Y7V

Structural analysis of MurU

Summary for 4Y7V

• Entry DOI: 10.2210/pdb4y7v/pdb
• Descriptor: Nucleotidyl transferase, GLYCEROL, SULFATE ION, ... (6 entities in total)
• Functional Keywords: nucleotidyltransferase family protein, uridyltransferase, rossman fold, murnac-1p, transferase
• Biological source: Pseudomonas putida (strain BIRD-1)
• Total number of polymer chains: 1
• Total formula weight: 25651.77

Authors

Renner-Schneck, M.G.,Stehle, T. (deposition date: 2015-02-16, release date: 2015-03-18, Last modification date: 2024-05-08)

Primary citation

Renner-Schneck, M.,Hinderberger, I.,Gisin, J.,Exner, T.,Mayer, C.,Stehle, T.
Crystal Structure of the N-Acetylmuramic Acid alpha-1-Phosphate (MurNAc-alpha 1-P) Uridylyltransferase MurU, a Minimal Sugar Nucleotidyltransferase and Potential Drug Target Enzyme in Gram-negative Pathogens.
J.Biol.Chem., 290:10804-10813, 2015

PubMed Abstract: The N-acetylmuramic acid α-1-phosphate (MurNAc-α1-P) uridylyltransferase MurU catalyzes the synthesis of uridine diphosphate (UDP)-MurNAc, a crucial precursor of the bacterial peptidoglycan cell wall. MurU is part of a recently identified cell wall recycling pathway in Gram-negative bacteria that bypasses the general de novo biosynthesis of UDP-MurNAc and contributes to high intrinsic resistance to the antibiotic fosfomycin, which targets UDP-MurNAc de novo biosynthesis. To provide insights into substrate binding and specificity, we solved crystal structures of MurU of Pseudomonas putida in native and ligand-bound states at high resolution. With the help of these structures, critical enzyme-substrate interactions were identified that enable tight binding of MurNAc-α1-P to the active site of MurU. The MurU structures define a "minimal domain" required for general nucleotidyltransferase activity. They furthermore provide a structural basis for the chemical design of inhibitors of MurU that could serve as novel drugs in combination therapy against multidrug-resistant Gram-negative pathogens.

PubMed: 25767118
DOI: 10.1074/jbc.M114.620989

Experimental method

X-RAY DIFFRACTION (1.8 Å)