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Crystal structure shows two main parts to the protein, but as a whole three independent molecules. There is a chromodomain and SET domain. The chromodomain starts at the N-terminus of the enzyme and continues toward the C-terminus, where the SET catalytic domain is located. The chromodomain length is around 44-106 amino acids long, which forms three anti- parallel beta sheets. The lengths for each of three beta sheets are 45-53, 58-64 and 73-76 amino acids long for beta 1, beta 2 and beta 3, respectively ( shown in figure 2). These three beta sheets form the chromodomain.
Crystal structure shows two main parts to the protein, but as a whole three independent molecules. There is a chromodomain and SET domain. The chromodomain starts at the N-terminus of the enzyme and continues toward the C-terminus, where the SET catalytic domain is located. The chromodomain length is around 44-106 amino acids long, which forms three anti- parallel beta sheets. The lengths for each of three beta sheets are 45-53, 58-64 and 73-76 amino acids long for beta 1, beta 2 and beta 3, respectively ( shown in figure 2). These three beta sheets form the chromodomain.
=== SET Structure ===
=== SET Structure ===
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The catylatic domain is consisted of a alpha doible helix. The double helix is located on the C-terminus end of the portein. The residue consisting the catylatic domain is about 82-100 amino acids long. In addition to the two main domains to the enzyme, there is an essential hydrophobic core which is very similar to other chromodomain proteins. The hydrophobic core is made up several residues. These reisdues are V45, L48, Y60, V62, W64, L80, I85 and L86 (each letter represents an amino acids). The similarity between the chromodomain of SUV39h1 and chromodomains of other enzymes is very similar. SUV39h1 has been shown to very similar to the chromoddomain of MPP8 and HP1, showing a conservation in chromodomain structure. although the chromodomain structure is very similar, there is a slight difference with the catylitic domain being longer. In addition to the catyltic domain of SUV39H1 being longer, The enzyme lacks a F34 aromatic cage, which was originally thought to be essential for recognizing exposed lysine or argon residue. However, residues of form a loop which binds to the exposed rsidues of the substrate, showing that it is not a conserved feature in the chromodomain family of enzymes.
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The catalytic domain is consisted of an alpha double helix. The double helix is located at the C-terminus end of the protein. The residue consisting the catalytic domain is about 82-100 amino acids long (Shown in Figure 2). The C-terminus is where the transfer of the methyl group to the lysine residue occurs. In addition to the two main domains to the enzyme, there is an essential hydrophobic core which is very similar to other chromodomain proteins. The hydrophobic core is made up several residues. These residues are V45, L48, Y60, V62, W64, L80, I85 and L86 (Shown in Figure 2). The groove formed by the beta sheets is also similar and conserved feature of the chromodomain family. The physical characteristics between the chromodomain of SUV39h1 and chromodomains of other enzymes are very similar. SUV39h1 has been shown to very similar to the chromodomain of MPP8 and HP1, showing a conservation in chromodomain structure (shown in Figure 3). Although the chromodomain structure is very similar, there is a slight difference with the catalytic domain being longer. In addition to the catalytic domain of SUV39H1 being longer, the enzyme contains a F34 aromatic cage, which was originally thought to be essential for recognizing exposed lysine or argon residue. However, crystallography of residues (44-106) has shown residues missing the F34 aromatic cage.
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Revision as of 19:00, 25 April 2013

==Your Heading Here (maybe something like 'Structure'-- PLEASE DO NOT DELETE THIS TEMPLATE -->

This Sandbox is Reserved from Feb 1, 2013, through May 10, 2013 for use in the course "Biochemistry" taught by Irma Santoro at the Reinhardt University. This reservation includes Sandbox Reserved 591 through Sandbox Reserved 599.
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Contents

Background

SUV39h1 is part of a class of methytransferase that deals with the methylation of histone proteins in nucleosomes. It is one of the very first histone methyltransferase to be discovered. The methylation of histone proteins is an essential part of an area of genetics which deals with the modification of histone proteins called epigenomics. Epigenomics is the study of modifications of nucleosomes, which either inhibit or express gene transcription without changing the underlining DNA sequence. These changes are allowed because of the amino acid tails which extend out and away from the histone proteins, exposing itself to methylation. Methylation of histone protein is one of many ways that regulates gene expression. The regulation of gene expression is dependent on the state of the gene. A gene cannot be transcribed when the promoter of the gene is wrapped around the nucleosome, forming a heterochromatin state; thus, the gene is inhibited from being transcribed. Conversely, Methylation of the histone protein causes the winding around the nucleosomes, transforming a euchromatin state into a heterochromatin state. Of course, SUV39H1 alone does not methylate the histone proteins. SUV39H1 interacts with other proteins in order to efficiently methylate a histone protein (shown in Figure 1). Abnormal expression of genes, which is the result of down regulation or mutation of SUV39H1, results in a variety of diseases.

Figure 1 showing the methylation of the histone protein and the subsequent formation of heterochromatin
Figure 1 showing the methylation of the histone protein and the subsequent formation of heterochromatin

Structure

Insert caption here

Drag the structure with the mouse to rotate

Chromodomain Structure

Crystal structure shows two main parts to the protein, but as a whole three independent molecules. There is a chromodomain and SET domain. The chromodomain starts at the N-terminus of the enzyme and continues toward the C-terminus, where the SET catalytic domain is located. The chromodomain length is around 44-106 amino acids long, which forms three anti- parallel beta sheets. The lengths for each of three beta sheets are 45-53, 58-64 and 73-76 amino acids long for beta 1, beta 2 and beta 3, respectively ( shown in figure 2). These three beta sheets form the chromodomain.

SET Structure

The catalytic domain is consisted of an alpha double helix. The double helix is located at the C-terminus end of the protein. The residue consisting the catalytic domain is about 82-100 amino acids long (Shown in Figure 2). The C-terminus is where the transfer of the methyl group to the lysine residue occurs. In addition to the two main domains to the enzyme, there is an essential hydrophobic core which is very similar to other chromodomain proteins. The hydrophobic core is made up several residues. These residues are V45, L48, Y60, V62, W64, L80, I85 and L86 (Shown in Figure 2). The groove formed by the beta sheets is also similar and conserved feature of the chromodomain family. The physical characteristics between the chromodomain of SUV39h1 and chromodomains of other enzymes are very similar. SUV39h1 has been shown to very similar to the chromodomain of MPP8 and HP1, showing a conservation in chromodomain structure (shown in Figure 3). Although the chromodomain structure is very similar, there is a slight difference with the catalytic domain being longer. In addition to the catalytic domain of SUV39H1 being longer, the enzyme contains a F34 aromatic cage, which was originally thought to be essential for recognizing exposed lysine or argon residue. However, crystallography of residues (44-106) has shown residues missing the F34 aromatic cage.

Figure 2 shows the residue and tertiary and Quaternary structure SUV39H1
Figure 2 shows the residue and tertiary and Quaternary structure SUV39H1



Function

SET Function

There are two types of histone methyltransferases: lysine specific and argine specific; each are residues which the enzyme transfers a mathyl 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. The cofactor is very important because it is the source of the methyl group.

Chromodomain function

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 results in the inhibition of the enzyme. 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. ---

Clinical relevence

A mutation in SUV39H1 encompass a wide variety of diseases. Most notably, however, SUV39H1 plays a huge role in cancer and inflammatory disease. Since SUV39H1 is part of a family of histone mthyltransferases, there is a potential use as an epigentic control.

Figure 3 showing the methylation of the histone protein and the subsequent formation of heterochromatin
Figure 3 showing the methylation of the histone protein and the subsequent formation of heterochromatin

References

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