A comparative analysis of the binding site of Plasmodium falciparum histone deacetylase-1 and human histone deacetylase-8

Abstract

Histone deacetylases (HDACs) are a family of enzymes involved in the modulation of mammalian cell chromatin structure,
regulation of gene expression, DNA repair, and stress response. The histone deacetylase enzymes Plasmodium falciparum
histone deacetylase-1 (PfHDAC-1) and human histone deacetylase-8(hHDAC 8) have been identified as novel targets for
development of antimalarial and antitumor drugs respectively. Homology models of PfHDAC-1 and hHDAC 8 were
generated from the crystal structures of HDAC8 and HDLP and IT64 respectively using a restraint guided optimization
procedure involving a combination of the Optimized Potentials for Liquid Simulations and the Generalized Born Surface
Area (OPLS/GBSA) potential setup. The models were validated using protein structure validation tools. Comparative
analysis of their binding sites was also carried out to identify their topology and residue interaction that could be utilized
in developing PfHDAC-1 specific inhibitors.