ArticleAngewandte Chemie (International ed. in English)2014
A designed conformational shift to control protein binding specificity.
Article in Angewandte Chemie (International ed. in English), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- ATP-independent unfolding of ubiquitin by Ufd1 initiates Cdc48/p97-mediated substrate processing.Nature structural & molecular biology · 2026Article
- Improving Conformational Ensembles of Folded Proteins in Go̅Martini.Journal of chemical theory and computation · 2026Article
- Solution structure of mouse HBS1L/SKI7-specific UBA domain in complex with ubiquitin: Implications for stalled ribosome recognition.PloS one · 2026Article
- Extending the detectable time window of fast protein dynamics usingJournal of biomolecular NMR · 2025Article
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.Structure (London, England : 1993) · 2023Article
- Fusion crystallization reveals the behavior of both the 1TEL crystallization chaperone and the TNK1 UBA domain.bioRxiv : the preprint server for biology · 2023Article
- Characterisation of the OTU domain deubiquitinase complement ofLife science alliance · 2023Article
- A litmus test for classifying recognition mechanisms of transiently binding proteins.Nature communications · 2022Article
- Structural-Energetic Basis for Coupling between Equilibrium Fluctuations and Phosphorylation in a Protein Native Ensemble.ACS central science · 2022Article
- Implementing and Assessing an Alchemical Method for Calculating Protein-Protein Binding Free Energy.Journal of chemical theory and computation · 2021Article
- The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63-branched ubiquitin chains.The EMBO journal · 2021Article
- Combining free energy calculations with tailored enzyme activity assays to elucidate substrate binding of a phospho-lysine phosphatase.Chemical science · 2020Article
- Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020Review
- Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.Nucleic acids research · 2020Article
- Membranes as the third genetic code.Molecular biology reports · 2020Review
- Large scale relative protein ligand binding affinities using non-equilibrium alchemy.Chemical science · 2019Article
- Role of Displacing Confined Solvent in the Conformational Equilibrium of β-Cyclodextrin.The journal of physical chemistry. B · 2019Article
- Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer.The Journal of biological chemistry · 2019Article
- Article
- Modulation of allosteric coupling by mutations: from protein dynamics and packing to altered native ensembles and function.Current opinion in structural biology · 2019Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding-competent substates.
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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.