Targeting IspD for Anti-infective and Herbicide Development: Exploring Its Role, Mechanism, and Structural Insights.

Antimicrobial resistance (AMR) and herbicide resistance pose threats to society, necessitating novel anti-infectives and herbicides exploiting untapped modes of action like inhibition of IspD, the third enzyme in the MEP pathway. The MEP pathway is essential for a wide variety of human pathogens, including , , and as well as plants. Within the current perspective, we focused our attention on the third enzyme in this pathway, IspD, offering a comprehensive summary of the reported modes of inhibition and common trends, with the goal to inspire future research dedicated to this underexplored target.

Efficacy and Safety of Mydriatic Microdrops for Retinopathy of Prematurity Screening: The MyMiROPS Randomized Clinical Trial.

Importance: Commercial mydriatics administered in preterm infants during retinopathy of prematurity (ROP) screening have been associated with various cardiorespiratory and gastrointestinal adverse events.

Objective: To examine whether microdrops of a combined mixture of 1.67% phenylephrine and 0.

Fragment Discovery by X-Ray Crystallographic Screening Targeting the CTP Binding Site of Pseudomonas Aeruginosa IspD.

With antimicrobial resistance (AMR) reaching alarming levels, new anti-infectives with unprecedented mechanisms of action are urgently needed. The 2-C-methylerythritol-D-erythritol-4-phosphate (MEP) pathway represents an attractive source of drug targets due to its essential role in numerous pathogenic Gram-negative bacteria and Mycobacterium tuberculosis (Mt), whilst being absent in human cells. Here, we solved the first crystal structure of Pseudomonas aeruginosa (Pa) IspD, the third enzyme in the MEP pathway and present the discovery of a fragment-based compound class identified through crystallographic screening of PaIspD.

Targeting the IspE Enzyme.

The enzyme IspE in is considered an attractive drug target, as it is essential for parasite survival and is absent in the human proteome. Yet it still has not been addressed by a small-molecule inhibitor. In this study, we conducted a high-throughput screening campaign against the IspE enzyme.

IspE kinase as an anti-infective target: Role of a hydrophobic pocket in inhibitor binding.

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.