4y7t
From Proteopedia
Structural analysis of MurU
Structural highlights
FunctionMURU_PSEPK Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc), a crucial precursor of the bacterial peptidoglycan cell wall, from UTP and MurNAc-alpha-1P (PubMed:23831760, PubMed:25767118). Is involved in peptidoglycan recycling as part of a cell wall recycling pathway that bypasses de novo biosynthesis of the peptidoglycan precursor UDP-MurNAc (PubMed:23831760). Plays a role in intrinsic resistance to fosfomycin, which targets the de novo synthesis of UDP-MurNAc (PubMed:23831760). Is not able to use GlcNAc-alpha-1P and GalNAc-alpha-1P as substrates (PubMed:23831760). Cannot accept other nucleotide triphosphates (ATP, CTP, TTP, or GTP) than UTP (PubMed:25767118).[1] [2] Publication Abstract from PubMedThe N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) 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-alpha1P 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, which could serve as novel drugs in combination therapy against multi-resistant Gram-negative pathogens. Crystal structure of the N-acetylmuramic acid alpha-1-phosphate (MurNAc-alpha1P) uridylytransferase MurU, a minimal sugar-nucleotidyltransferase and potential drug target enzyme in Gram-negative pathogens.,Renner-Schneck M, Hinderberger I, Gisin J, Exner T, Mayer C, Stehle T J Biol Chem. 2015 Mar 12. pii: jbc.M114.620989. PMID:25767118[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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