Substrate Competitive GSK-3 Inhibitors strategy and Implications
| Autor: | Shmuel Pietrokovski, Hagit Eldar-Finkelman, Avital Licht-Murava, Miriam Eisenstein |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Biophysics
macromolecular substances Computational biology Biology Biochemistry Substrate Specificity Analytical Chemistry Serine Glycogen Synthase Kinase 3 GSK-3 Diabetes Mellitus Animals Humans Protein kinase A Glycogen synthase Protein Kinase Inhibitors Molecular Biology chemistry.chemical_classification Kinase Drug discovery Neurodegenerative Diseases Enzyme chemistry biology.protein Phosphorylation |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1804:598-603 |
| ISSN: | 1570-9639 |
| DOI: | 10.1016/j.bbapap.2009.09.010 |
| Popis: | Glycogen synthase kinase-3 (GSK-3) is a highly conserved protein serine/threonine kinase ubiquitously distributed in eukaryotes as a constitutively active enzyme. Abnormally high GSK-3 activity has been implicated in several pathological disorders, including diabetes and neuron degenerative and affective disorders. This led to the hypothesis that inhibition of GSK-3 may have therapeutic benefit. Most GSK-3 inhibitors developed so far compete with ATP and often show limited specificity. Our goal is to develop inhibitors that compete with GSK-3 substrates, as this type of inhibitor is more specific and may be useful for clinical applications. We have employed computational, biochemical, and molecular analyses to gain in-depth understanding of GSK-3's substrate recognition. Here we argue that GSK-3 is a promising drug discovery target and describe the strategy and practice for developing specific substrate-competitive inhibitors of GSK-3. |
| Databáze: | OpenAIRE |
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