Artikel ; Online: Comparative modeling and dynamic simulation of UDP-N-acetylmuramoyl-alanine ligase (MurC) from Mycobacterium tuberculosis through virtual screening and toxicity analysis.
2020 Band 262, Seite(n) 118466
Abstract: Introduction: UDP-N-acetylmuramic-alanine ligase (MurC) is an enzyme catalyzing the addition of L-alanine to UDP-acetylmuramoyl nucleotide precursor in Mycobacterium tuberculosis (M. tuberculosis). This enzyme is a prerequisite for the biosynthesis of ... ...
| Abstract | Introduction: UDP-N-acetylmuramic-alanine ligase (MurC) is an enzyme catalyzing the addition of L-alanine to UDP-acetylmuramoyl nucleotide precursor in Mycobacterium tuberculosis (M. tuberculosis). This enzyme is a prerequisite for the biosynthesis of the peptidoglycans in M. tuberculosis. Aim: This study aimed to identify the novel inhibitors of MurC using in silico approach. Materials and methods: The three dimensional (3D) structure of MurC was determined using comparative modeling and based on the template obtained from Haemophilus influenza (1P31). The structural analysis of the model structure shown that three residues (Lys126, Glu170, and Glu358) are critical for in the catalytic activity of the enzyme, and their inhibition will block the function of the enzyme. Ten thousand and ninety-five (10095) compounds obtained through virtual screening against Zinc and PubChem databases based on their ability to bind to MurC with minimum binding energies. These ligands screened for the physicochemical properties, molecular docking, and pharmacokinetic analyses. Finding: Six compounds had desirable physicochemical and pharmacokinetic properties with excellent binding energy ranged between -12.27 and -10.09 kcal/mol. These compounds subjected to Molecular Dynamic (MD) Simulation and Molecular Mechanics Generalized Born Surface Area (MM-GBSA) analyses. The outcome of the analysis revealed that four ligands (PubChem1548994, ZINC11882115, ZINC22241774, and ZINC12330603) formed a stable conformation in the substrate-binding site of the protein during the 50 ns MD simulation. Conclusion: Therefore, the ligands mentioned above might regard as novel inhibitors of M. tuberculosis which requires further in vitro and in vivo validation. |
|---|---|
| Mesh-Begriff(e) | Antitubercular Agents/chemistry ; Antitubercular Agents/pharmacokinetics ; Antitubercular Agents/pharmacology ; Binding Sites ; Ligands ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/enzymology ; Peptide Synthases/antagonists & inhibitors ; Peptide Synthases/chemistry ; Protein Binding |
| Chemische Substanzen | Antitubercular Agents ; Ligands ; Peptide Synthases (EC 6.3.2.-) ; UDP-N-acetylmuramoylalanine-D-glutamate ligase (EC 6.3.2.9) |
| Sprache | Englisch |
| Erscheinungsdatum | 2020-09-19 |
| Erscheinungsland | Netherlands |
| Dokumenttyp | Comparative Study ; Journal Article |
| ZDB-ID | 3378-9 |
| ISSN | 1879-0631 ; 0024-3205 |
| ISSN (online) | 1879-0631 |
| ISSN | 0024-3205 |
| DOI | 10.1016/j.lfs.2020.118466 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
| Uc I Zs.368: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.