ArticleBiophysical journal2015
How an Inhibitor Bound to Subunit Interface Alters Triosephosphate Isomerase Dynamics.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- RinPy, a Python Package for Residue Interaction Network Model to Analyze Protein Structures and Predict Ligand Binding Sites.Journal of chemical information and modeling · 2026Article
- Guanidines: Privileged Scaffolds Against Neglected Tropical Diseases: A Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Breaking glycolysis: allosteric hotspots for multi-target drug repurposing.Journal of computer-aided molecular design · 2026Article
- A Computationally Efficient Method to Generate Plausible Conformers for Ensemble Docking and Binding Free Energy Calculations.Journal of chemical information and modeling · 2025Article
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Mechanism-based and computational modeling of hydrogen sulfide biogenesis inhibition: interfacial inhibition.Scientific reports · 2023Article
- Ligand-Based Virtual Screening and Molecular Docking of Benzimidazoles as Potential Inhibitors of Triosephosphate Isomerase Identified New Trypanocidal Agents.International journal of molecular sciences · 2022Article
- Precise druggability of the PTH type 1 receptor.Nature chemical biology · 2022Article
- Sampling of Protein Conformational Space Using Hybrid Simulations: A Critical Assessment of Recent Methods.Frontiers in molecular biosciences · 2022Article
- Phenylbenzothiazole derivatives: effects against a Trypanosoma cruzi infection and toxicological profiles.Parasitology research · 2021Article
- Virtual Screening of FDA-Approved Drugs against Triose Phosphate Isomerase fromInternational journal of molecular sciences · 2021Article
- Intrinsic dynamics is evolutionarily optimized to enable allosteric behavior.Current opinion in structural biology · 2020Review
- Essential site scanning analysis: A new approach for detecting sites that modulate the dispersion of protein global motions.Computational and structural biotechnology journal · 2020Article
- Identification of Alternative Allosteric Sites in Glycolytic Enzymes for Potential Use as Species-Specific Drug Targets.Frontiers in molecular biosciences · 2020Article
- Phenylpyrrole fungicides act on triosephosphate isomerase to induce methylglyoxal stress and alter hybrid histidine kinase activity.Scientific reports · 2019Article
- Novel and SelectiveVeterinary sciences · 2018Article
- Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma brucei: Kinetic and Molecular Dynamics Studies.Molecules (Basel, Switzerland) · 2017Article
- Transcriptome analysis of dormant tomonts of the marine fish ectoparasitic ciliate Cryptocaryon irritans under low temperature.Parasites & vectors · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tunnel region at triosephosphate isomerase (TIM)'s dimer interface, distant from its catalytic site, is a target site for certain benzothiazole derivatives that inhibit TIM's catalytic activity in Trypanosoma cruzi, the parasite that causes Chagas disease. We performed multiple 100-ns molecular-dynamics (MD) simulations and elastic network modeling (ENM) on both apo and complex structures to shed light on the still unclear inhibitory mechanism of one such inhibitor, named bt10. Within the time frame of our MD simulations, we observed stabilization of aromatic clusters at the dimer interface and enhancement of intersubunit hydrogen bonds in the presence of bt10, which point to an allosteric effect rather than destabilization of the dimeric structure. The collective dynamics dictated by the topology of TIM is known to facilitate the closure of its catalytic loop over the active site that is critical for substrate entrance and product release. We incorporated the ligand's effect on vibrational dynamics by applying mixed coarse-grained ENM to each one of 54,000 MD snapshots. Using this computationally efficient technique, we observed altered collective modes and positive shifts in eigenvalues due to the constraining effect of bt10 binding. Accordingly, we observed allosteric changes in the catalytic loop's dynamics, flexibility, and correlations, as well as the solvent exposure of catalytic residues. A newly (to our knowledge) introduced technique that performs residue-based ENM scanning of TIM revealed the tunnel region as a key binding site that can alter global dynamics of the enzyme.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.