About Histone Deacetylases / HDAC:
Histone Deacetylases which is also commonly known as HDAC is best regarded as a class of enzymes. This particular class completely removes acetyl groups from lysine amino acid. Due to this, histones are able to wrap around DNA more tightly. As this occurs expression of DNA becomes regulated by both acetylation and e-acetylation. It is actually the opposite of the impact of historic acetyltransferases. These proteins are often now referred to as KDAC or lysine deacetylases. This is used to describe the function rather than their particular target.
Histone Deacetylases has two main functions. These are histone modification and non-the histone effects. It is worth noting that regulating gene transcription through the modification of both chromatin structure and histones is the main function. However, there are other particular modifications that are of particular relevance.
For instance, protein phosphorylation is widely studied and largely understood. Here amino acids are phosphorylated through the particular action of protein kinases. It can also occur through the dephosphorylated action from phosphatases.
Histones also tend to be positively charged and this is largely due to the amine groups that are present on arginine and lysine amino acids. These ensure that the histones to interact and thus bind with the phosphate groups on the DNA backbone which are negatively charged. The binding and potential decreased binding provides the option of chromatin expansion which inturn permits genetic transcription to take place.
Histone Deacetylases Structure
Currently, there have been x-ray crystal structures of four human HDACs. These are 2, 4 7 as well as 8. There are also structures for three HDAC related deacetylase-like amidohydrolase which is also known as HDAH and acetylpolyamine amidohydrolase (APAH).
It’s worth noting that when comparing the structures of these enzymes’ studies have shown that there is a conserved constellation made up of active site residues. Further structural analysis of the structures of these will determine guidelines for particular tight-binding inhibitors as well as the potential future prospects of developing isozyme-specific inhibitors. Studies suggest that the possibilities are incredibly promising.
The structure of the Histone Deacetylase provides evidence of a common mechanism that is shared between the metal-dependent hydrolysis for active substrates. It is also important to note that there are different classes of these enzymes. Class III enzymes are believed to have a different mechanism of action and are NAD+ dependent. In contrast, HDACs throughout other classes will typically require a Zn2 for a particular cofactor.
Studies have also explored the analogous mechanism by which non-histone proteins may be enacted upon by both deacetylases and acetylases.
Histone Deacetylases Interactions
Histone deacetylase is involved in a wide variety of interactions. For instance. FUS interacts directly with histone deacetylase 1 and plays a pivotal role in the DNA damage response. Furthermore, there is also a reduced level of interaction with HDAC1 during recombinational DNA repair.