2y67

New 5-Benzylidenethiazolidine-4-one Inhibitors of Bacterial MurD Ligase: Design, Synthesis, Crystal Structures, and Biological Evaluation

spinqualitylabelsall models 2y67, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y67 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: N21, SO4 NonStd Res: KCX Related: 2uuo, 2jfg, 4uag, 2uag, 3uag, 1e0d, 2vte, 2jff, 1eeh, 2x5o, 2wjp, 2vtd, 2y1o, 1uag, 2jfh, 2uup, 2y66, 2y68 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 Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC(50) values up to 28muM. Inhibitor 37, with an IC(50) of 34muM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128mug/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation.,Zidar N, Tomasic T, Sink R, Kovac A, Patin D, Blanot D, Contreras-Martel C, Dessen A, Premru MM, Zega A, Gobec S, Masic LP, Kikelj D Eur J Med Chem. 2011 Sep 17. PMID:21963114 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Mur ligase

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