2y68

Structure-based design of a new series of D-glutamic acid-based inhibitors of bacterial MurD ligase

spinqualitylabelsall models 2y68, resolution 1.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y68 is a 1 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AZI, CL, DMS, SO4, T04 NonStd Res: KCX Related: 2uuo, 2jfg, 4uag, 2uag, 3uag, 1e0d, 2x5o, 1eeh, 2jff, 2vte, 2wjp, 2vtd, 2y1o, 1uag, 2jfh, 2uup, 2y66, 2y67 Activity: UDP-N-acetylmuramoyl-L-alanine--D-glutamate ligase, with EC number 6.3.2.9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MURD_ECOLI] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639] Publication Abstract from PubMed MurD ligase is one of the key enzymes participating in the intracellular steps of peptidoglycan biosynthesis and constitutes a viable target in the search for novel antibacterial drugs to combat bacterial drug-resistance. We have designed, synthesized, and evaluated a new series of d-glutamic acid-based Escherichia coli MurD inhibitors incorporating the 5-benzylidenethiazolidin-4-one scaffold. The crystal structure of 16 in the MurD active site has provided a good starting point for the design of structurally optimized inhibitors 73-75 endowed with improved MurD inhibitory potency (IC(50) between 3 and 7 muM). Inhibitors 74 and 75 showed weak activity against Gram-positive Staphylococcus aureus and Enterococcus faecalis. Compounds 73-75, with IC(50) values in the low micromolar range, represent the most potent d-Glu-based MurD inhibitors reported to date. Structure-Based Design of a New Series of d-Glutamic Acid Based Inhibitors of Bacterial UDP-N-acetylmuramoyl-l-alanine:d-glutamate Ligase (MurD).,Tomasic T, Zidar N, Sink R, Kovac A, Blanot D, Contreras-Martel C, Dessen A, Muller-Premru M, Zega A, Gobec S, Kikelj D, Peterlin Masic L J Med Chem. 2011 Jun 3. PMID:21591605 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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