4JMN

Crystal structure of LD transpeptidase LdtMt1 from M. tuberculosis

4JMN の概要

• エントリーDOI: 10.2210/pdb4jmn/pdb
• 関連するPDBエントリー: 4JMX
• 分子名称: Probable L,D-transpeptidase LdtA (2 entities in total)
• 機能のキーワード: ig-like domain and beta barrel, cell wall modelling, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23640.57

構造登録者

Ruggiero, A.,Correale, S.,Berisio, R. (登録日: 2013-03-14, 公開日: 2013-10-23, 最終更新日: 2024-02-28)

主引用文献

Correale, S.,Ruggiero, A.,Capparelli, R.,Pedone, E.,Berisio, R.
Structures of free and inhibited forms of the L,D-transpeptidase LdtMt1 from Mycobacterium tuberculosis.
Acta Crystallogr.,Sect.D, 69:1697-1706, 2013

PubMed Abstract: The modelling of peptidoglycan is responsible for key cellular processes in Mycobacterium tuberculosis such as cell growth, division and resuscitation from dormancy. The structure of M. tuberculosis peptidoglycan is atypical since it contains a majority of 3,3 cross-links synthesized by L,D-transpeptidases that replace the 4,3 cross-links formed by the D,D-transpeptidase activity of classical penicillin-binding proteins. Carbapenems inactivate these L,D-transpeptidases and in combination with clavulanic acid are bactericidal against extensively drug-resistant M. tuberculosis. Here, crystal structures of the L,D-transpeptidase LdtMt1 from M. tuberculosis in a ligand-free form and in complex with the carbapenem imipenem are reported. Elucidation of the structural features of LdtMt1 unveils analogies and differences between the two key transpeptidases of M. tuberculosis: LdtMt1 and LdtMt2. In addition, the structure of imipenem-inactivated LdtMt1 provides a detailed structural view of the interactions between a carbapenem drug and LdtMt1. By providing the key interactions in the binding of carbapenem to LdtMt1, this work will facilitate structure-guided discovery of L,D-transpeptidase inhibitors as novel antitubercular agents against drug-resistant M. tuberculosis.

PubMed: 23999293
DOI: 10.1107/S0907444913013085

実験手法

X-RAY DIFFRACTION (2.2 Å)