3VMQ

Crystal structure of Staphylococcus aureus membrane-bound transglycosylase: Apoenzyme

3VMQ の概要

• エントリーDOI: 10.2210/pdb3vmq/pdb
• 関連するPDBエントリー: 3VMR 3VMS 3VMT
• 分子名称: Monofunctional glycosyltransferase, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: transmembrane, glycosyltransferase, bacterial cell wall synthesis, membrane, transferase
• 由来する生物種: Staphylococcus aureus
• 細胞内の位置: Cell membrane; Single-pass membrane protein (By similarity): Q99T05
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 60653.04

構造登録者

Huang, C.Y.,Shih, H.W.,Lin, L.Y.,Tien, Y.W.,Cheng, T.J.R.,Cheng, W.C.,Wong, C.H.,Ma, C. (登録日: 2011-12-15, 公開日: 2012-04-18, 最終更新日: 2023-11-08)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.518 Å)