3vms

Crystal structure of Staphylococcus aureus membrane-bound transglycosylase in complex with NBD-Lipid II

spinqualitylabelsall models 3vms, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3vms is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus Mu50. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.202Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MGT_STAAM 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 transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, and many antibiotics have been developed to target the transpeptidase; however, the problem of antibiotic resistance has arisen and caused a major threat in bacterial infection. The transglycosylase has been considered to be another excellent target, but no antibiotics have been developed to target this enzyme. Here, we determined the crystal structure of the Staphylococcus aureus membrane-bound transglycosylase, monofunctional glycosyltransferase, in complex with a lipid II analog to 2.3 A resolution. Our results showed that the lipid II-contacting residues are not only conserved in WT and drug-resistant bacteria but also significant in enzymatic activity. Mechanistically, we proposed that K140 and R148 in the donor site, instead of the previously proposed E156, are used to stabilize the pyrophosphate-leaving group of lipid II, and E100 in the acceptor site acts as general base for the 4-OH of GlcNAc to facilitate the transglycosylation reaction. This mechanism, further supported by mutagenesis study and the structure of monofunctional glycosyltransferase in complex with moenomycin in the donor site, provides a direction for antibacterial drugs design. Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism.,Huang CY, Shih HW, Lin LY, Tien YW, Cheng TJ, Cheng WC, Wong CH, Ma C Proc Natl Acad Sci U S A. 2012 Apr 24;109(17):6496-501. Epub 2012 Apr 9. PMID:22493270 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycosyltransferase 3D structures

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