3VMS

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

Summary for 3VMS

• Entry DOI: 10.2210/pdb3vms/pdb
• Related: 3VMQ 3VMR 3VMT
• Descriptor: Monofunctional glycosyltransferase (1 entity in total)
• Functional Keywords: transmembrane, glycosyltransferase, bacterial cell wall synthesis, membrane, transferase
• Biological source: Staphylococcus aureus
• Cellular location: Cell membrane; Single-pass membrane protein (By similarity): Q99T05
• Total number of polymer chains: 2
• Total formula weight: 60628.74

Authors

Huang, C.Y.,Shih, H.W.,Lin, L.Y.,Tien, Y.W.,Cheng, T.J.R.,Cheng, W.C.,Wong, C.H.,Ma, C. (deposition date: 2011-12-15, release date: 2012-04-18, Last modification date: 2023-11-08)

Primary citation

Huang, C.Y.,Shih, H.W.,Lin, L.Y.,Tien, Y.W.,Cheng, T.J.R.,Cheng, W.C.,Wong, C.H.,Ma, C.
Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism
Proc.Natl.Acad.Sci.USA, 109:6496-6501, 2012

PubMed Abstract: 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 Å 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.

PubMed: 22493270
DOI: 10.1073/pnas.1203900109

Experimental method

X-RAY DIFFRACTION (3.202 Å)