Journal of Molecular Modeling

, Volume 18, Issue 3, pp 1063–1072 | Cite as

Virtual screening for potential inhibitors of bacterial MurC and MurD ligases

  • Tihomir Tomašić
  • Andreja Kovač
  • Gerhard Klebe
  • Didier Blanot
  • Stanislav Gobec
  • Danijel Kikelj
  • Lucija Peterlin Mašič
Original Paper

Abstract

Mur ligases are bacterial enzymes involved in the cytoplasmic steps of peptidoglycan biosynthesis and are viable targets for antibacterial drug discovery. We have performed virtual screening for potential ATP-competitive inhibitors targeting MurC and MurD ligases, using a protocol of consecutive hierarchical filters. Selected compounds were evaluated for inhibition of MurC and MurD ligases, and weak inhibitors possessing dual inhibitory activity have been identified. These compounds represent new scaffolds for further optimisation towards multiple Mur ligase inhibitors with improved inhibitory potency.

Figure

Structure and predicted binding mode of dual 1,3,5-triazine-based inhibitor in E. coli MurC and MurD active sites

Keywords

ATP Inhibitor Multiple ligand Mur ligase Pharmacophore Virtual screening 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Tihomir Tomašić
    • 1
  • Andreja Kovač
    • 1
  • Gerhard Klebe
    • 2
  • Didier Blanot
    • 3
  • Stanislav Gobec
    • 1
  • Danijel Kikelj
    • 1
  • Lucija Peterlin Mašič
    • 1
  1. 1.Faculty of PharmacyUniversity of LjubljanaLjubljanaSlovenia
  2. 2.Institut für Pharmazeutische ChemiePhilipps Universität MarburgMarburgGermany
  3. 3.Enveloppes Bactériennes et Antibiotiques, IBBMC, UMR 8619 CNRS, Univ Paris-SudOrsayFrance

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