Recent developments on UDP-N-acetylmuramoyl-L-alanine-D-gutamate ligase (Mur D) enzyme for antimicrobial drug development: An emphasis on in-silico approaches

Gaur, Vinita; Bera, Surojit

doi:10.1016/j.crphar.2022.100137

Cited by 4 publications

(1 citation statement)

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“…This begins with MurC, which catalyzes the addition of L-Ala to UDP-MurNAc, forming UDP-MurNAc-L-Ala. This is followed by the addition of D-Glu, catalyzed by MurD, resulting in UDP-MurNAc-L-Ala-D-Glu [ 10 , 11 ]. Further, MurE catalyzes the addition of meso-Diaminopimelic acid (m-DAP), producing a tripeptide which is further catalyzed by MurF and adds D-Ala-D-Ala moiety to it, thereby generating UDP-MurNAc-L-Ala-D-Glu-m-DAP-D-Ala-D-Ala [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Tuberculosis Mur Inhibitors: Structural Insights and the Way Ahead for Development of Novel Agents

et al. 2023

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Mur enzymes serve as critical molecular devices for the synthesis of UDP-MurNAc-pentapeptide, the main building block of bacterial peptidoglycan polymer. These enzymes have been extensively studied for bacterial pathogens such as Escherichia coli and Staphylococcus aureus. Various selective and mixed Mur inhibitors have been designed and synthesized in the past few years. However, this class of enzymes remains relatively unexplored for Mycobacterium tuberculosis (Mtb), and thus offers a promising approach for drug design to overcome the challenges of battling this global pandemic. This review aims to explore the potential of Mur enzymes of Mtb by systematically scrutinizing the structural aspects of various reported bacterial inhibitors and implications concerning their activity. Diverse chemical scaffolds such as thiazolidinones, pyrazole, thiazole, etc., as well as natural compounds and repurposed compounds, have been reviewed to understand their in silico interactions with the receptor or their enzyme inhibition potential. The structural diversity and wide array of substituents indicate the scope of the research into developing varied analogs and providing valuable information for the purpose of modifying reported inhibitors of other multidrug-resistant microorganisms. Therefore, this provides an opportunity to expand the arsenal against Mtb and overcome multidrug-resistant tuberculosis.

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Section: Introductionmentioning

confidence: 99%