8A4D

1-deoxy-D-xylulose 5-phosphate synthase from Pseudomonas aeruginosa with a thiamine analog inhibitor

8A4D の概要

• エントリーDOI: 10.2210/pdb8a4d/pdb
• 分子名称: 1-deoxy-D-xylulose-5-phosphate synthase, 2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]phenyl}ethanol, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Pseudomonas aeruginosa LESB58; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 405354.63

構造登録者

Hamid, R.,Hirsch, A. (登録日: 2022-06-10, 公開日: 2023-07-12, 最終更新日: 2024-02-07)

主引用文献

Hamid, R.,Adam, S.,Lacour, A.,Monjas, L.,Kohnke, J.,Hirsch, A.K.H.
1-deoxy-D-xylulose-5-phosphate synthase from Pseudomonas aeruginosa and Klebsiella pneumoniae reveals conformational changes upon cofactor binding.
J.Biol.Chem., 299:105152-105152, 2023

PubMed Abstract: The ESKAPE bacteria are the six highly virulent and antibiotic-resistant pathogens that require the most urgent attention for the development of novel antibiotics. Detailed knowledge of target proteins specific to bacteria is essential to develop novel treatment options. The methylerythritol-phosphate (MEP) pathway, which is absent in humans, represents a potentially valuable target for the development of novel antibiotics. Within the MEP pathway, the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXPS) catalyzes a crucial, rate-limiting first step and a branch point in the biosynthesis of the vitamins B1 and B6. We report the high-resolution crystal structures of DXPS from the important ESKAPE pathogens Pseudomonas aeruginosa and Klebsiella pneumoniae in both the co-factor-bound and the apo forms. We demonstrate that the absence of the cofactor thiamine diphosphate results in conformational changes that lead to disordered loops close to the active site that might be important for the design of potent DXPS inhibitors. Collectively, our results provide important structural details that aid in the assessment of DXPS as a potential target in the ongoing efforts to combat antibiotic resistance.

PubMed: 37567475
DOI: 10.1016/j.jbc.2023.105152

実験手法

X-RAY DIFFRACTION (2.2 Å)