ArticleAngewandte Chemie (International ed. in English)2014
Discovery of selective small-molecule activators of a bacterial glycoside hydrolase.
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 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- A small molecule allosterically activates SecA dependent secretion.Communications biology · 2026Article
- Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase.Chembiochem : a European journal of chemical biology · 2023Article
- Heliorhodopsin binds and regulates glutamine synthetase activity.PLoS biology · 2022Article
- Synthesis and Evaluation of Novel Iminosugars Prepared from Natural Amino Acids.Molecules (Basel, Switzerland) · 2021Article
- Amino Acid-Based Synthesis and Glycosidase Inhibition of Cyclopropane-Containing Iminosugars.ACS omega · 2020Article
- Fragment-derived modulators of an industrial β-glucosidase.The Biochemical journal · 2020Article
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- RUNX2-modifying enzymes: therapeutic targets for bone diseases.Experimental & molecular medicine · 2020Review
- Article
- Small-Molecule Activators of Glucose-6-phosphate Dehydrogenase (G6PD) Bridging the Dimer Interface.ChemMedChem · 2019Article
- Galactose as novel target against Acanthamoeba cysts.PLoS neglected tropical diseases · 2019Article
- Current perspectives in fragment-based lead discovery (FBLD).Essays in biochemistry · 2017Review
- Increase of enzyme activity through specific covalent modification with fragments.Chemical science · 2017Article
- Uncoupling conformational states from activity in an allosteric enzyme.Nature communications · 2017Article
- Insights into activity and inhibition from the crystal structure of human O-GlcNAcase.Nature chemical biology · 2017Article
- Biophysics in drug discovery: impact, challenges and opportunities.Nature reviews. Drug discovery · 2016Review
- Twenty years on: the impact of fragments on drug discovery.Nature reviews. Drug discovery · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fragment-based approaches are used routinely to discover enzyme inhibitors as cellular tools and potential therapeutic agents. There have been few reports, however, of the discovery of small-molecule enzyme activators. Herein, we describe the discovery and characterization of small-molecule activators of a glycoside hydrolase (a bacterial O-GlcNAc hydrolase). A ligand-observed NMR screen of a library of commercially available fragments identified an enzyme activator which yielded an approximate 90 % increase in kcat /KM values (kcat =catalytic rate constant; KM =Michaelis constant). This compound binds to the enzyme in close proximity to the catalytic center. Evolution of the initial hits led to improved compounds that behave as nonessential activators effecting both KM and Vmax values (Vmax =maximum rate of reaction). The compounds appear to stabilize an active "closed" form of the enzyme. Such activators could offer an orthogonal alternative to enzyme inhibitors for perturbation of enzyme activity in vivo, and could also be used for glycoside hydrolase activation in many industrial processes.
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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.