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

Daan Willocx1,2, Eleonora Diamanti1, Anna K H Hirsch1,3,2

  • 1Helmholtz Institute for Pharmaceutical Research (HIPS)-Helmholtz Centre for Infection Research (HZI), Saar-land University, Campus E8.1, 66123Saarbrücken, Germany.

Journal of Medicinal Chemistry
|January 3, 2025
PubMed

Insights

Novel anti-infectives and herbicides targeting IspD, an enzyme in the MEP pathway, are crucial for combating antimicrobial resistance (AMR) and herbicide resistance. This review explores IspD inhibition strategies for developing new therapeutics and agrochemicals.

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Plant Science

Background:

  • Antimicrobial resistance (AMR) and herbicide resistance present significant global challenges.
  • The Methylerythritol Phosphate (MEP) pathway is essential for various pathogens and plants.
  • IspD, the third enzyme in the MEP pathway, represents an underexplored target for novel interventions.

Purpose of the Study:

  • To provide a comprehensive summary of IspD inhibition modes and trends.
  • To inspire future research on IspD as a therapeutic and agrochemical target.
  • To offer an overview of IspD's history, mechanism, and structure.

Main Methods:

  • Literature review of reported IspD inhibition strategies.
  • Analysis of common trends in IspD inhibition.
  • Compilation of information on IspD's catalytic mechanism and structure.

Main Results:

  • Identified various modes of inhibition for the IspD enzyme.
  • Highlighted common trends in the development of IspD inhibitors.
  • Detailed the enzyme's catalytic mechanism and structural features.

Conclusions:

  • IspD is a promising target for developing new anti-infectives and herbicides.
  • Further research into IspD inhibition can lead to novel solutions for AMR and herbicide resistance.
  • Understanding IspD's characteristics facilitates the design of effective inhibitors.

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