4Y7T
Structural analysis of MurU
Summary for 4Y7T
| Entry DOI | 10.2210/pdb4y7t/pdb |
| Descriptor | Nucleotidyl transferase, GLYCEROL, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | nucleotidyltransferase family protein, uridyltransferase, rossman fold, transferase |
| Biological source | Pseudomonas putida |
| Total number of polymer chains | 1 |
| Total formula weight | 25481.81 |
| 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 Cited by 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: 25767118DOI: 10.1074/jbc.M114.620989 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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