Introduction

Histones

Histones are a family of basic, positively charged proteins that associate with DNA inside the nucleus to help condense the DNA into chromatin ^[1]. The nuclear DNA is wrapped around the histone in order to fit in the nucleus. Nucleosomes are chromatin beads made up of DNA wrapped around eight histone proteins, or a histone octamer ^[1]. Four different examples of modifying histones including Histone acetylation, Histone deacetylation, Histone methylation and Histone demethylation ^[1].

Histone Deacetylases (HDACs)

ε-Amino-lysine acetylation is a type of histone modification that controls the stability of proteins and biological function in eukaryotic cells ^[2]. Histone Deacetylation is the reversal process for this acetylation modification. There are different classes of HDACs based on phylogenetic analysis:

•Class I - HDACs 1-3 and 8, which are homologous to yeast Rpd3

•Class II - HDACs 4-7, 9 and 10, which are homologous to yeast Hda1

•Class III - Sirtuin deacetylases

•Class IV - HDAC 11 ^[2].

HDACs 1-11 are metalloenzymes and require a zinc ion for deacetylation ^[2].

HDAC8

Histone Deacetylase 8 is

Structure

General Structure Information

Inhibitor

Potassium Binding Site

Deacetylation

Zn²⁺ Metal Ion Mechanism

Figure 1. Mechanism of HDAC8

Active Site

Disease

HDACis