8PXZ

Crystal structure of the transpeptidase LdtMt2 from Mycobacterium tuberculosis in complex with natural substrate

8PXZ の概要

• エントリーDOI: 10.2210/pdb8pxz/pdb
• 分子名称: L,D-transpeptidase 2, Peptidoglycan tripeptide, Peptidoglycan dipeptide, ... (7 entities in total)
• 機能のキーワード: ldtmt2, substrate complex, mycobacterium tuberculosis, l, d-transpeptidase, antimicrobial protein
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 38901.52

構造登録者

de Munnik, M.,Schofield, C.J. (登録日: 2023-07-24, 公開日: 2024-08-07, 最終更新日: 2024-10-16)

主引用文献

de Munnik, M.,Lang, P.A.,Calvopina, K.,Rabe, P.,Brem, J.,Schofield, C.J.
Biochemical and crystallographic studies of L,D-transpeptidase 2 from Mycobacterium tuberculosis with its natural monomer substrate.
Commun Biol, 7:1173-1173, 2024

PubMed Abstract: The essential L,D-transpeptidase of Mycobacterium tuberculosis (Ldt) catalyses the formation of 3 3 cross-links in cell wall peptidoglycan and is a target for development of antituberculosis therapeutics. Efforts to inhibit Ldt have been hampered by lack of knowledge of how it binds its substrate. To address this gap, we optimised the isolation of natural disaccharide tetrapeptide monomers from the Corynebacterium jeikeium bacterial cell wall through overproduction of the peptidoglycan sacculus. The tetrapeptides were used in binding / turnover assays and biophysical studies on Ldt We determined a crystal structure of wild-type Ldt reacted with its natural substrate, the tetrapeptide monomer of the peptidoglycan layer. This structure shows formation of a thioester linking the catalytic cysteine and the donor substrate, reflecting an intermediate in the transpeptidase reaction; it informs on the mode of entrance of the donor substrate into the Ldt active site. The results will be useful in design of Ldt inhibitors, including those based on substrate binding interactions, a strategy successfully employed for other nucleophilic cysteine enzymes.

PubMed: 39294212
DOI: 10.1038/s42003-024-06785-3

実験手法

X-RAY DIFFRACTION (1.98 Å)