6IYW

Crystal sturucture of L,D-transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with Imipenem adduct

6IYW の概要

• エントリーDOI: 10.2210/pdb6iyw/pdb
• 関連するPDBエントリー: 3VYO 3VYP
• 分子名称: L,D-transpeptidase 2, (5R)-5-[(1S,2R)-1-formyl-2-hydroxypropyl]-3-[(2-{[(E)-iminomethyl]amino}ethyl)sulfanyl]-4,5-dihydro-1H-pyrrole-2-carbox ylic acid, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ld-transpeptidase, peptidoglycan synthesis enzyme, beta-lactam binding, transferase
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 181334.59

構造登録者

Li, D.F.,Zhao, F.,Wang, D.C. (登録日: 2018-12-17, 公開日: 2019-02-27, 最終更新日: 2024-11-13)

主引用文献

Zhao, F.,Hou, Y.J.,Zhang, Y.,Wang, D.C.,Li, D.F.
The 1-beta-methyl group confers a lower affinity of l,d-transpeptidase LdtMt2 for ertapenem than for imipenem.
Biochem. Biophys. Res. Commun., 510:254-260, 2019

PubMed Abstract: L,D-transpeptidases, widely distributed in bacteria and even in the difficult-to-treat ESKAPE pathogens, can confer antibacterial resistance against the traditional β-lactam antibiotics through bypass of the 4 → 3 transpeptide linkage. Ldt, a l,d-transpeptidase in Mycobacteria tuberculosis, is essential for bacterial virulence and is considered as a potential anti-tuberculosis target inhibited by carbapenems. Diverse interaction modes between carbapenems and Ldt have been reported, there are only limited evidences to validate those interaction modes. Herein, we identified the stable binding states of two carbapenems, imipenem and ertapenem, via crystallographic and biochemical studies, discovered that they adopt similar binding conformations. We further demonstrate the absence of the 1-β-methyl group in imipenem and the presence of both Y308 and Y318 residues in Ldt synergistically resulted in one order of magnitude higher affinity for imipenem than ertapenem. Our study provides a structural basis for the rational drug design and evolvement of novel carbapenems against bacterial L,D-transpeptidases.

PubMed: 30686533
DOI: 10.1016/j.bbrc.2019.01.082

実験手法

X-RAY DIFFRACTION (1.6 Å)