Alternative Modes of Binding of Recombinant Human Histone Deacetylase 8 to Colloidal Gold Nanoparticles
Histone deacetylases are intimately involved in the transcriptional regulation of genes, and they are high priority drug targets for cancer therapy. Due to prevalence of several sulfhydryl groups on the surface of histone deacetylase 8, we explored the possibility of its binding to colloidal gold nanoparticles by determining its potentials to inhibit the flocculation as well as retaining the enzyme activity. It was observed that although both these processes conformed to the binding affinity of the gold-histone deacetylase 8 conjugate as being equal to 15–20 nM, only 30% of the nanoparticle-bound enzyme exhibited the enzymatic activity. In the light of the structural features of histone deacetylase 8, we propose that the enzyme interacts with the gold nanoparticles via the surface exposed thiol groups, and such interaction occurs in two alternative modes. Whereas the enzyme bound via mode-1 is catalytically inactive (presumably due to the orientation of the enzyme's active site toward the gold nanoparticle surface), and it prevents the flocculation of the nanoparticles, the enzyme bound via mode-2 shows the full catalytic activity (as its active site is believed to be oriented away from the nanoparticle surface). Although the histone deacetylase 8 bound to AuNP via mode-2 exhibits the same inhibitory potency against Trichostatin A as the free enzyme, the former is more susceptible to thermal denaturation. The potential of potent interaction between gold nanoparticles and histone deacetylase 8 via alternative modes may find diagnostic and/or therapeutic applications for different forms of cancers.
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Document Type: Research Article
Publication date: 2008-12-01
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