8QCC

E.coli IspE in complex with a ligand (1)

8QCC の概要

• エントリーDOI: 10.2210/pdb8qcc/pdb
• 分子名称: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, ADENOSINE-5'-DIPHOSPHATE, ~{N}-[3-[4-azanyl-2-oxidanylidene-1-[(2~{R})-thiolan-2-yl]pyrimidin-5-yl]prop-2-ynyl]cyclopropanesulfonamide, ... (5 entities in total)
• 機能のキーワード: e. coli, ispe, inhibitor, complex., transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 63591.41

構造登録者

Hamid, R. (登録日: 2023-08-25, 公開日: 2024-09-11, 最終更新日: 2025-03-26)

主引用文献

Hamid, R.,Walsh, D.J.,Diamanti, E.,Aguilar, D.,Lacour, A.,Hamed, M.M.,Hirsch, A.K.H.
IspE kinase as an anti-infective target: Role of a hydrophobic pocket in inhibitor binding.
Structure, 32:2390-2398.e2, 2024

PubMed Abstract: Enzymes of the methylerythritol phosphate (MEP) pathway are potential targets for antimicrobial drug discovery. Here, we focus on 4-diphosphocytidyl-2-C-methyl-D-erythritol (IspE) kinase from the MEP pathway. We use biochemical and structural biology methods to investigate homologs from pathogenic microorganisms; Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. We determined the X-ray crystal structures of IspE-inhibitor complexes and studied inhibitors' binding modes targeting the substrate pocket. The experimental results indicate the need for distinct inhibitor strategies due to structural differences among IspE homologs, particularly for A. baumannii IspE, which displays a unique inhibitory profile due to a tighter hydrophobic subpocket in the substrate binding site. This study enhances our understanding of the MEP enzymes and sets the stage for structure-based drug design of selective inhibitors to combat pathogenic microorganisms.

PubMed: 39510075
DOI: 10.1016/j.str.2024.10.009

実験手法

X-RAY DIFFRACTION (1.9 Å)