ArticleeLife2019
The dynamic conformational landscape of the protein methyltransferase SETD8.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed.
- In Silico Isomerization Produces Apt Negative Data for VHTS Validation.Journal of chemical information and modeling · 2026Article
- APC coordinates GSK3 phosphorylation of SETD8 to suppress colorectal cancer.Cell reports · 2026Article
- Discovery of a Potent, Selective, and In Vivo Efficacious Covalent Inhibitor for Lysine Methyltransferase SETD8.Journal of medicinal chemistry · 2026Article
- Assembling Ternary Dead-End Complex for Covalent Trapping of Protein Lysine Methyltransferases.Journal of the American Chemical Society · 2026Article
- SGSS05-NS3, a covalent SETD8 inhibitor that activates p53 pathway in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2025Article
- Opening and closing of a cryptic pocket in VP35 toggles it between two different RNA-binding modes.eLife · 2025Article
- Structure-Based Virtual Screening of Potential Inhibitors Targeting the Prolyl-tRNA Synthetase (PRS) inMolecules (Basel, Switzerland) · 2025Article
- Accounting for Fast vs Slow Exchange in Single Molecule FRET Experiments Reveals Hidden Conformational States.Journal of chemical theory and computation · 2024Article
- Accounting for fast vs slow exchange in single molecule FRET experiments reveals hidden conformational states.bioRxiv : the preprint server for biology · 2024Article
- Article
- PopShift: A Thermodynamically Sound Approach to Estimate Binding Free Energies by Accounting for Ligand-Induced Population Shifts from a Ligand-Free Markov State Model.Journal of chemical theory and computation · 2024Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Folding@home: Achievements from over 20 years of citizen science herald the exascale era.Biophysical journal · 2023Review
- Folding@home: achievements from over twenty years of citizen science herald the exascale era.ArXiv · 2023Article
- Mechanistic basis of the increased methylation activity of the SETD2 protein lysine methyltransferase towards a designed super-substrate peptide.Communications chemistry · 2022Article
- Roles for the methyltransferase SETD8 in DNA damage repair.Clinical epigenetics · 2022Review
- In silico identification of novel SARS-COV-2 2'-O-methyltransferase (nsp16) inhibitors: structure-based virtual screening, molecular dynamics simulation and MM-PBSA approaches.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Opening of a cryptic pocket in β-lactamase increases penicillinase activity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Profiling and Validation of Live-Cell Protein Methylation with Engineered Enzymes and Methionine Analogues.Current protocols · 2021Article
- SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome.Nature chemistry · 2021Article
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
Elucidating the conformational heterogeneity of proteins is essential for understanding protein function and developing exogenous ligands. With the rapid development of experimental and computational methods, it is of great interest to integrate these approaches to illuminate the conformational landscapes of target proteins. SETD8 is a protein lysine methyltransferase (PKMT), which functions in vivo via the methylation of histone and nonhistone targets. Utilizing covalent inhibitors and depleting native ligands to trap hidden conformational states, we obtained diverse X-ray structures of SETD8. These structures were used to seed distributed atomistic molecular dynamics simulations that generated a total of six milliseconds of trajectory data. Markov state models, built via an automated machine learning approach and corroborated experimentally, reveal how slow conformational motions and conformational states are relevant to catalysis. These findings provide molecular insight on enzymatic catalysis and allosteric mechanisms of a PKMT via its detailed conformational landscape.
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Registered trials
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.