8QCO

E.coli IspE in complex with a ligand (3)

Summary for 8QCO

• Entry DOI: 10.2210/pdb8qco/pdb
• Descriptor: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, ADENOSINE-5'-DIPHOSPHATE, ~{N}-[3-(4-azanyl-2-oxidanylidene-1~{H}-pyrimidin-5-yl)prop-2-ynyl]cyclopentanesulfonamide, ... (4 entities in total)
• Functional Keywords: e. coli, ispe, inhibitor, complex, kinase, transferase
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 63353.67

Authors

Hamid, R. (deposition date: 2023-08-28, release date: 2024-09-11, Last modification date: 2025-03-26)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.55 Å)