3VAE

Crystal Structure of M. tuberculosis LD-transpeptidase type 2 with Modified Catalytic Cysteine (C354)

3VAE の概要

• エントリーDOI: 10.2210/pdb3vae/pdb
• 分子名称: LD-transpeptidase type 2, DI(HYDROXYETHYL)ETHER (3 entities in total)
• 機能のキーワード: protein-peptidoglycan complex, peptidoglycan binding protein
• 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: 2
• 化学式量合計: 62499.32

構造登録者

Erdemli, S.,Bianchet, M.A.,Gupta, R.,Lamichhane, G.,Amzel, L.M. (登録日: 2011-12-29, 公開日: 2012-12-12, 最終更新日: 2024-10-30)

主引用文献

Erdemli, S.B.,Gupta, R.,Bishai, W.R.,Lamichhane, G.,Amzel, L.M.,Bianchet, M.A.
Targeting the Cell Wall of Mycobacterium tuberculosis: Structure and Mechanism of L,D-Transpeptidase 2.
Structure, 20:2103-2115, 2012

PubMed Abstract: With multidrug-resistant cases of tuberculosis increasing globally, better antibiotic drugs and novel drug targets are becoming an urgent need. Traditional β-lactam antibiotics that inhibit D,D-transpeptidases are not effective against mycobacteria, in part because mycobacteria rely mostly on L,D-transpeptidases for biosynthesis and maintenance of their peptidoglycan layer. This reliance plays a major role in drug resistance and persistence of Mycobacterium tuberculosis (Mtb) infections. The crystal structure at 1.7 Å resolution of the Mtb L,D-transpeptidase Ldt(Mt2) containing a bound peptidoglycan fragment, reported here, provides information about catalytic site organization as well as substrate recognition by the enzyme. Based on our structural, kinetic, and calorimetric data, we propose a catalytic mechanism for Ldt(Mt2) in which both acyl-acceptor and acyl-donor substrates reach the catalytic site from the same, rather than different, entrances. Together, this information provides vital insights to facilitate development of drugs targeting this validated yet unexploited enzyme.

PubMed: 23103390
DOI: 10.1016/j.str.2012.09.016

実験手法

X-RAY DIFFRACTION (2.8 Å)