6FTB

Staphylococcus aureus monofunctional glycosyltransferase in complex with moenomycin

6FTB の概要

• エントリーDOI: 10.2210/pdb6ftb/pdb
• 関連するPDBエントリー: 2C6W 2OLU 2OLV 2ZC5 3DWK 3HZS
• 分子名称: Monofunctional glycosyltransferase, MOENOMYCIN, 1,2-ETHANEDIOL, ... (6 entities in total)
• 機能のキーワード: transglycosylase, peptidoglycan, monofunctional, moenomycin, inhibitor, membrane, cell shape, cell wall biosynthesis, glycosyltransferase, peptidoglycan synthesis, transferase, antibiotics
• 由来する生物種: Staphylococcus aureus MW2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30092.58

構造登録者

Punekar, A.S.,Dowson, C.J.,Roper, D.I. (登録日: 2018-02-20, 公開日: 2018-06-27, 最終更新日: 2024-01-17)

主引用文献

Punekar, A.S.,Samsudin, F.,Lloyd, A.J.,Dowson, C.G.,Scott, D.J.,Khalid, S.,Roper, D.I.
The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization.
Cell Surf, 2:54-66, 2018

PubMed Abstract: Bacterial peptidoglycan glycosyltransferases (PGT) catalyse the essential polymerization of lipid II into linear glycan chains required for peptidoglycan biosynthesis. The PGT domain is composed of a large head subdomain and a smaller jaw subdomain and can be potently inhibited by the antibiotic moenomycin A (MoeA). We present an X-ray structure of the MoeA-bound monofunctional PGT enzyme, revealing electron density for a second MoeA bound to the jaw subdomain as well as the PGT donor site. Isothermal titration calorimetry confirms two drug-binding sites with markedly different affinities and positive cooperativity. Hydrophobic cluster analysis suggests that the membrane-interacting surface of the jaw subdomain has structural and physicochemical properties similar to amphipathic cationic -helical antimicrobial peptides for lipid II recognition and binding. Furthermore, molecular dynamics simulations of the drug-free and -bound forms of the enzyme demonstrate the importance of the jaw subdomain movement for lipid II selection and polymerization process and provide molecular-level insights into the mechanism of peptidoglycan biosynthesis by PGTs.

PubMed: 30046666
DOI: 10.1016/j.tcsw.2018.06.002

実験手法

X-RAY DIFFRACTION (2.1 Å)