6ftb | pdb_00006ftb

Staphylococcus aureus monofunctional glycosyltransferase in complex with moenomycin

spinqualitylabelsall models 6ftb, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ftb is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1QW, EDO, M0E, PO4 Related: 3hzs, 2c6w, 2zc5, 2olu, 3dwk, 2olv Activity: Peptidoglycan glycosyltransferase, with EC number 2.4.1.129 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [MGT_STAAW] Involved in the biosynthesis of cell wall peptidoglycan. Responsible for the elongation of the glycan strands using lipid-linked disaccharide-pentapeptide as the substrate (By similarity). Publication Abstract from PubMed Bacterial cell wall transglycosylases (TGs) and transpeptidases (TPs) are ideal drug targets due to their essentiality, accessibility and lack of mammalian homologs. Although antibacterial therapy using the beta-lactam family of TP inhibitors has been successful for decades, potent TG inhibitors which are suitable for development into antibiotics for human use have yet to be identified. We sought to further understand the molecular interactions required to inhibit bacterial transglycosylation by characterizing the active site of Staphylococcus aureus (Sa) monofunctional transglycosylase (Mtg). Ten mutants were tested for their ability to polymerize Lipid II and to crystallize in the presence of moenomycin. Five of six putative active site mutants (E100Q, D101N, Q136E, E156T, and Y176F) were found to be catalytically inactive whereas a F104Y mutation did not affect activity. Four mutants generated to enhance crystal formation (F143T, V154T, L157T, and F158T) also retained activity. Here we also report the crystal structure of Sa Mtg E100Q mutant in complex with the inhibitor moenomycin to 2.1A resolution. The co-crystal structure revealed detailed interactions between the protein and inhibitor including portions of the polycarbon tail of moenomycin. The structure also contained an ordered phosphate ion which helped to identify the Lipid II binding site. Characterization of the active site of S. aureus monofunctional glycosyltransferase (Mtg) by site-directed mutation and structural analysis of the protein complexed with moenomycin.,Heaslet H, Shaw B, Mistry A, Miller AA J Struct Biol. 2009 Aug;167(2):129-35. Epub 2009 May 3. PMID:19416756 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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