7A9G

Truncated 1-deoxy-D-xylulose 5-phosphate synthase (DXS) from Mycobacterium tuberculosis with intermediate 2-acetyl-thiamine diphosphate

これはPDB形式変換不可エントリーです。

7A9G の概要

• エントリーDOI: 10.2210/pdb7a9g/pdb
• 関連するPDBエントリー: 7A9H
• 分子名称: 1-deoxy-D-xylulose-5-phosphate synthase,1-deoxy-D-xylulose-5-phosphate synthase, 2-ACETYL-THIAMINE DIPHOSPHATE, MAGNESIUM ION, ... (9 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Mycobacterium tuberculosis H37Rv; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 145389.98

構造登録者

Gierse, R.M.,Reddem, E.,Grooves, M.R. (登録日: 2020-09-02, 公開日: 2022-03-23, 最終更新日: 2024-01-31)

主引用文献

Gierse, R.M.,Oerlemans, R.,Reddem, E.R.,Gawriljuk, V.O.,Alhayek, A.,Baitinger, D.,Jakobi, H.,Laber, B.,Lange, G.,Hirsch, A.K.H.,Groves, M.R.
First crystal structures of 1-deoxy-D-xylulose 5-phosphate synthase (DXPS) from Mycobacterium tuberculosis indicate a distinct mechanism of intermediate stabilization.
Sci Rep, 12:7221-7221, 2022

PubMed Abstract: The development of drug resistance by Mycobacterium tuberculosis and other pathogenic bacteria emphasizes the need for new antibiotics. Unlike animals, most bacteria synthesize isoprenoid precursors through the MEP pathway. 1-Deoxy-D-xylulose 5-phosphate synthase (DXPS) catalyzes the first reaction of the MEP pathway and is an attractive target for the development of new antibiotics. We report here the successful use of a loop truncation to crystallize and solve the first DXPS structures of a pathogen, namely M. tuberculosis (MtDXPS). The main difference found to other DXPS structures is in the active site where a highly coordinated water was found, showing a new mechanism for the enamine-intermediate stabilization. Unlike other DXPS structures, a "fork-like" motif could be identified in the enamine structure, using a different residue for the interaction with the cofactor, potentially leading to a decrease in the stability of the intermediate. In addition, electron density suggesting a phosphate group could be found close to the active site, provides new evidence for the D-GAP binding site. These results provide the opportunity to improve or develop new inhibitors specific for MtDXPS through structure-based drug design.

PubMed: 35508530
DOI: 10.1038/s41598-022-11205-9

実験手法

X-RAY DIFFRACTION (1.9 Å)