Sandbox Reserved 592: Difference between revisions

There are two types of histone methyltransferases: lysine specific and argine specific; each is a residue which the enzyme transfers a methyl group to. Within the lysine specific, there are further two main types: SET (Su(var)3-9, Enhancer of Zeste, Trithorax) and non-SET domains. These domains are an essential part of the enzyme because the main catalytic occurs in SET domain of the methyltransferase. SUV39h1 is considered to have a lysine specific SET domain which catalyzes the methyltransferase. In the nucleosomes, there are four different proteins; each consists of two copies which make the entire nucleosome. The mechanism by which SUV39H1 methylates the histone proteins is also known. A nearby tyrosine residue in the histone protein creates a strong nucleophile by deprotonating a nearby lysine residue in the same histone protein. The lysine residue is a very strong nucleophile which attacks the sulfur atom of the cofactor S-Adensyl methoinine (SAM) and extracts a methyl group from the cofactor. Subsequently, the attack methylates the histone protein (Shown in Figure 4). The cofactor is very important because it is the source of the methyl group.<ref>PMID:12372303</ref>

The chromodomain structure of the enzyme (residues) is not involve in the catalytic function of the enzyme, but is very important to the binding to the molecule. Mutations which remove the chromodomain area of the enzyme result in the inhibition of the enzyme1 <ref>PMID:6519522</ref>. The inhibition of the chromodomain prevents the methylating action of the enzyme's catalytic domain. Although the chromodomain is not directly involved in the methylation of the histone proteins, it plays an important role in the binding of the enzyme to histone proteins as well as other proteins. Fluorescence Polarization Assays have shown the chromodomain has a high affinity for the histone protein H3K9me1 and H3K9me2. SUV39H1 residues that did not contain the aromatic F34 cage did not bind to the histone protein. This shows the F34 is a conserved residue that is essential for the enzyme binding to the histone protein. Moreover, a mutation which results in the loss of the aromatic F34 cage group will inhibit the binding effect of the chromodomain enzymes. SUV39H1 does not methylate the histone protein alone; it is aided by other proteins. Studies have shown HP1 and H3 are essential proteins that combine with SUV39H1 in protein complex, which methylate the histone protein of a nucleosome <ref>PMID:12565857</ref>.

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