5DU7

Crystal structure of ldtMt2 at 1.79 Angstrom resolution

5DU7 の概要

• エントリーDOI: 10.2210/pdb5du7/pdb
• 関連するPDBエントリー: 5DUJ
• 分子名称: L,D-transpeptidase 2 (2 entities in total)
• 機能のキーワード: peptidoglycan synthesis enzyme, cell wall enzyme, transferase
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cell membrane ; Lipid-anchor : O53223
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 158128.02

構造登録者

Kumar, P.,Lamichhane, G. (登録日: 2015-09-18, 公開日: 2016-09-28, 最終更新日: 2023-09-27)

主引用文献

Kumar, P.,Kaushik, A.,Lloyd, E.P.,Li, S.G.,Mattoo, R.,Ammerman, N.C.,Bell, D.T.,Perryman, A.L.,Zandi, T.A.,Ekins, S.,Ginell, S.L.,Townsend, C.A.,Freundlich, J.S.,Lamichhane, G.
Non-classical transpeptidases yield insight into new antibacterials.
Nat. Chem. Biol., 13:54-61, 2017

PubMed Abstract: Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the β-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of β-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for β-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria. We have characterized the molecular mechanisms responsible for inhibition of L,D-transpeptidases of Mycobacterium tuberculosis and a range of bacteria including ESKAPE pathogens, and used this information to design, synthesize and test simplified carbapenems with potent antibacterial activity.

PubMed: 27820797
DOI: 10.1038/nchembio.2237

実験手法

X-RAY DIFFRACTION (1.79 Å)