ArticlePloS one2015
Structure, dynamics, and interaction of Mycobacterium tuberculosis (Mtb) DprE1 and DprE2 examined by molecular modeling, simulation, and electrostatic studies.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Article
- Bibliometric and Visualization Analysis of DprE1 Inhibitors to Combat Tuberculosis.Drug design, development and therapy · 2025Article
- Molecular modeling, simulation and docking of Rv1250 protein fromFrontiers in bioinformatics · 2023Article
- Phylodynamics and Coat Protein Analysis of Babaco Mosaic Virus in Ecuador.Plants (Basel, Switzerland) · 2022Article
- Synthesis of Novel Derivatives of 5,6,7,8-Tetrahydroquinazolines Using α-Aminoamidines and In Silico Screening of Their Biological Activity.International journal of molecular sciences · 2022Article
- The Regulation of ManLAM-Related Gene Expression inInfection and drug resistance · 2022Article
- Anti-tuberculosis drug developmentFrontiers in microbiology · 2022Review
- The deleterious impact of a non-synonymous SNP on protein structure and function is apparent in hypertension.Journal of molecular modeling · 2021Article
- Chemical Space Exploration of DprE1 Inhibitors Using Chemoinformatics and Artificial Intelligence.ACS omega · 2021Article
- Molecular Docking Suggests the Targets of Anti-Mycobacterial Natural Products.Molecules (Basel, Switzerland) · 2021Article
- Identification of Novel Cyclin A2 Binding Site and Nanomolar Inhibitors of Cyclin A2-CDK2 Complex.Current computer-aided drug design · 2021Article
- Computational investigation for modeling the protein-protein interaction of TasAJournal of molecular modeling · 2020Article
- Screening of Natural Products Targeting SARS-CoV-2-ACE2 Receptor Interface - A MixMD Based HTVS Pipeline.Frontiers in chemistry · 2020Article
- The Molecular Basis of JAZ-MYC Coupling, a Protein-Protein Interface Essential for Plant Response to Stressors.Frontiers in plant science · 2020Article
- Metabolism of SKLB-TB1001, a Potent Antituberculosis Agent, in Animals.Antimicrobial agents and chemotherapy · 2018Article
- Successful Identification of Cardiac Troponin Calcium Sensitizers Using a Combination of Virtual Screening and ROC Analysis of Known Troponin C Binders.Journal of chemical information and modeling · 2017Article
- Structural and inhibition analysis of novel sulfur-rich 2-mercaptobenzothiazole and 1,2,3-triazole ligands against Mycobacterium tuberculosis DprE1 enzyme.Journal of molecular modeling · 2017Article
- Role of inhibitors of serine peptidases in protecting Leishmania donovani against the hydrolytic peptidases of sand fly midgut.Parasites & vectors · 2017Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The enzymes decaprenylphosphoryl-β-D-ribose oxidase (DprE1) and decaprenylphosphoryl-β-D-ribose-2-epimerase (DprE2) catalyze epimerization of decaprenylphosporyl ribose (DPR) todecaprenylphosporyl arabinose (DPA) and are critical for the survival of Mtb. Crystal structures of DprE1 so far reported display significant disordered regions and no structural information is known for DprE2. We used homology modeling, protein threading, molecular docking and dynamics studies to investigate the structural and dynamic features of Mtb DprE1 and DprE2 and DprE1-DprE2 complex. A three-dimensional model for DprE2 was generated using the threading approach coupled with ab initio modeling. A 50 ns simulation of DprE1 and DprE2 revealed the overall stability of the structures. Principal Component Analysis (PCA) demonstrated the convergence of sampling in both DprE1 and DprE2. In DprE1, residues in the 269-330 area showed considerable fluctuation in agreement with the regions of disorder observed in the reported crystal structures. In DprE2, large fluctuations were detected in residues 95-113, 146-157, and 197-226. The study combined docking and MD simulation studies to map and characterize the key residues involved in DprE1-DprE2 interaction. A 60 ns MD simulation for DprE1-DprE2 complex was also performed. Analysis of data revealed that the docked complex is stabilized by H-bonding, hydrophobic and ionic interactions. The key residues of DprE1 involved in DprE1-DprE2 interactions belong to the disordered region. We also examined the docked complex of DprE1-BTZ043 to investigate the binding pocket of DprE1 and its interactions with the inhibitor BTZ043. In summary, we hypothesize that DprE1-DprE2 interaction is crucial for the synthesis of DPA and DprE1-DprE2 complex may be a new therapeutic target amenable to pharmacological validation. The findings have important implications in tuberculosis (TB) drug discovery and will facilitate drug development efforts against TB.
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