Inactivating mutation in histone deacetylase 3 stabilizes its active conformation
| Autor: | Arrar, Mehrnoosh, de Oliveira, Cesar Augusto F, McCammon, J Andrew |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Protein Structure
Secondary conformational selection Proline Inositol Phosphates Biophysics Arginine Histone Deacetylases Models Catalytic Domain Enzyme Stability Genetics Humans Other Information and Computing Sciences Cancer R265P allostery Molecular HDAC3 Computation Theory and Mathematics Enzyme Activation Molecular Docking Simulation Amino Acid Substitution Mutation molecular recognition Biochemistry and Cell Biology Missense |
| Zdroj: | Arrar, M; De Oliveira, CAF; & McCammon, JA. (2013). Inactivating mutation in histone deacetylase 3 stabilizes its active conformation. Protein Science, 22(10), 1306-1312. doi: 10.1002/pro.2317. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/6q856415 Protein science : a publication of the Protein Society, vol 22, iss 10 |
| DOI: | 10.1002/pro.2317. |
| Popis: | Histone deacetylases (HDACs), together with histone acetyltransferases (HATs), regulate gene expression by modulating the acetylation level of chromatin. HDAC3 is implicated in many important cellular processes, particularly in cancer cell proliferation and metastasis, making inhibition of HDAC3 a promising epigenetic treatment for certain cancers. HDAC3 is activated upon complex formation with both inositol tetraphosphate (IP4) and the deacetylase-activating domain (DAD) of multi-protein nuclear receptor corepressor complexes. In previous studies, we have shown that binding of DAD and IP4 to HDAC3 significantly restricts its conformational space towards its stable ternary complex conformation, and suggest this to be the active conformation. Here, we report a single mutation of HDAC3 that is capable of mimicking the stabilizing effects of DAD and IP4, without the presence of either. This mutation, however, results in a total loss of deacetylase activity, prompting a closer evaluation of our understanding of the activation of HDAC3. © 2013 The Protein Society. |
| Databáze: | OpenAIRE |
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