Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors
Article Abstract:
Histone deacetylases (HDACs) play an important part in the regulation of gene expression and nucleosome conformation. They are involved in cell-cycle differentiation and progression, and their deregulation is associated with tumorigenesis. HDAC inhibitors, such as suberoylanilide hydroxamic acid and trichostatin, can inhibit cell growth and prevent tumour formation. A new study investigates the structure of the HDAC core. The deacetylase, deacetylase-TSA and deacetylase-SAHA structures show a zinc-binding site, a tubular pocket and two Asp-His charge-relay systems.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1999
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A structural basis for mutational inactivation of the tumour suppressor Smad4
Article Abstract:
The tumour suppressor Smad4/DPC4 is inhibited in almost half of pancreatic carcinomas. It belongs to the SMAD protein family that enable signalling by the TGF-beta/activin/BMP-2-4 cytokine superfamily. The conserved carboxy-terminal domains of SMADs can induce most ligand-specific effects. The crystal structure of the C-terminal domain of the Smad4/DPC4 tumour suppressor is described.
Publication Name: Nature
Subject: Zoology and wildlife conservation
ISSN: 0028-0836
Year: 1997
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