2mh5

Structure and NMR assignments of lantibiotic NAI-107 in DPC micelles

spinqualitylabelsall models 2mh5, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2mh5 is a 1 chain structure with sequence from Mics0. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DPV NonStd Res: 5CW, DAL, DBB, DBU, DHA, HYP, TEE Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA). To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance. The lantibiotic efficiently interfered with late stages of cell biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N- acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Using membrane preparations and a complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes (MraY, MurG, FemX, PBP2) and their respective purified substrates, we showed that NAI-107 forms complexes with bactoprenol- pyrophosphate coupled precursors of the bacterial cell wall. Titration experiments indicate that first a 1:1 stoichiometric complex occurs, which then transforms into a 2:1 (peptide : lipid II) complex, when excess peptide is added. Furthermore, lipid II and related molecules obviously could not serve as anchor molecules for the formation of defined and stable nisin-like pores, however slow membrane depolarization was observed after NAI-107 treatment, which could contribute to killing of the bacterial cell. The lantibiotic NAI-107 binds to bactoprenol bound cell wall precursors and impairs membrane functions.,Munch D, Muller A, Schneider T, Kohl B, Wenzel M, Bandow JE, Maffioli S, Sosio M, Donadio S, Wimmer R, Sahl HG J Biol Chem. 2014 Mar 13. PMID:24627484 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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