Chigozie's Fun With Jolecule

Ribonuclease

            Ribonuclease is the enzyme that digests RNA. It is a type of nuclease that catalyzes the degradation of RNA into smaller components. Ribonuclease is small, stable, and easily purified and has been an important enzyme in biochemical research. Ribonuclease can be divided into two groups: endoribonucleases and exoribonucleases. Endoribonucleases break down RNA from the middle through cleaving while exoribonucleases break down RNA from the 3’ or 5’ ends. Ribonuclease cleans cells of RNA that is no longer required and plays a key role in the maturing of RNA molecules such as messenger RNA and non-coding RNA. Also, ribonuclease acts as a first defense against RNA viruses and is the building block of more advanced immune strategies in cells. Because of ribonuclease’s nature to break down RNA, RNA in the cells has to be protected from ribonuclease. Defense mechanisms such as 5' end capping, 3'end polyadenylation, and folding within an RNA protein complex are implemented in cells. The alpha helices in this tertiary structure contain glycine which is the simplest amino acid with just an amino group, a carboxyl group and two hydrogen atoms. The glycine helps maintain structural alignment on the interior of ribonuclease as it breaks down RNA.

This is a close up on the tertiary structure of ribonuclease. Here one can see the alpha helices and the beta sheets that make up ribonuclease.

This is the catalytic part of the ribonuclease enzyme. Asp10, Glu48, Asp70, Asp134, and His124 can all be found in this area. These all contribute to catalysis in the enzyme by coordinating divalent metal ions that need to be present in order for the cleavage of RNA to be carried out. This would most likely be found in endoribonucleases.

This is a close up of an alpha helix in ribonuclease. This alpha helix contains glycine, which is important for the maintenance of structural alignment in ribonuclease. This glycine also adds to flexibility in this region.

Daphne's Fun With Jolecule

To begin, I went to http://jolecule.appspot.com, where I clicked on "Myglobin" to view a sample protein structure. I then decided that during this activity, I would primarily analyze lysozyme, which is a bacterial wall digestor. This enzyme manages to break through bacterial walls by catalyzing hydrolysis through the addition of water molecules. Lysozyme is an enzyme which is quite abundant in fluid secretions of animals, as it acts as a protectorate against bacteria. The function of lysozyme proteins is to break down the polysaccharide chain by the process of hydrolysis. The structure of this protein is what enables it to perform this function. The structure is partially beta strand and partially alpha helices. The differential between the two (which are primarily concentrated on their own) occurs where the molecule bonds to the sugar. The amino acid side chains glutamic acid 35 and aspartic acid 52 are known to be critical in the function of this protein. Because the amino acid Glu35 is located at the end of the beta strand, it is able to break down the polysaccharide train by breaking off molecules to form water molecules. A mature lysozyme molecule contains 128 amino acids. With these amino acids, lysozyme is able to hydrolyze a beta-glycosidic linkage between the N-acetylmuramic adic and N-acetyl glucosamine within the polypeptide chain located in the bacterial cell walls of invading specimen. Lysozyme is an incredibly important enzyme, as it helps to fight off bacterial infections which could otherwise be harmful to the inhabitants.

The full view of the lysozyme molecule. The polysaccharide substrate is at the
bottom right of the image. It is shown here without H2O molecules, as it would
be before it performs hydrolysis on a bacterial wall.

Here, the lysozyme molecule is pictured with water molecules added, as they
would be when the molecule bonds to a bacterial wall through the process of
hydrolysis. The polysaccharide substrate is at the bottom right of this image as
well. Note how H2O Molecules are heavily concentrated near the
polysaccharide chain, where bonding occurs between the lysozyme protein and
the bacterial wall.

This image is showint the polysaccharide chain attatched to the protein
lysozyme

The critical molecule Glutamic acid 35 shown as the bonding site between
the protein lysozome and the polysaccharide

 Works Cited

"Lysozyme." - Worthington Enzyme Manual. N.p., n.d. Web. 08 Nov. 2014.

Rana's Fun with Jolecule

Lysozymes

            In order to explore protein structures I went onto a protein model visualizer, called Jolecule, on http://jolecule.appspot.com/.  Once on the main page, I clicked on the “myoglobin” button, and then the “garden” link in the upper right corner.  This last link brought me to a variety of proteins to select from and learn about.  After I have looked through them, I chose to research the Lysozyme protein. 

            Lysozymes are small protein enzymes that bind to polysaccharide chains and break them apart by hydrolysis.  These enzymes protect humans from danger of bacterial infection by attacking and destroying the cell walls of the bacteria.  The bacteria itself constructs a tough skin of carbohydrate chains (sugars) that are interconnected by short peptide strands.  In order to fight the bacteria, the lysozyme breaks the carbohydrate chains of the bacteria, which in turn, destroys the structural integrity of the cell wall and causes the bacteria to burst.  However, as efficient as it is in killing bacteria, the lysozyme is too large of a molecule to travel between cells, that it cannot rid the entire body of disease.  Lysozymes occur in plant and animal tissues and in secretions such as tears, saliva and mucus.  Also it is greatly found in egg whites.  It is found in our tears, and mucus to resist infection on exposed surfaces.  Lysozyme also provides protection in the blood because blood is the worst place for bacteria to grow.  In general Lysozymes protect many places that are rich in potential food for bacteria.  As well, Lysozyme is added to digest cell debris and release the inclusion bodies. 

Furthermore, Lysozyme is a crystal structure with two structural domains.  One is made up of mainly alpha helices, and the other is mainly beta strands.  The boundary between the two domains forms a split where the substrate binds.  Lysozyme adds a molecule of water to the bond between two sugars, which breaks the bond.  This is catalyzed by two amino acid side chains in the active site of the enzyme.  These active sites are glutamate 35 and aspartate 52.  

- This is the overall picture of the lysozyme protein with the polysaccharide substrate in the center.

- This is one of the glu-35 active sites of the enzyme, which would lie next to the polysaccharide.  

- This is one of the asp-52 active sites of the enzyme, which would lie next to the polysaccharide.  

Jazmean's Fun with Jolecule

Glucocorticoid Receptor

After playing around in Jolecule, I decided to learn more about the different proteins they had available for viewing. The protein that peeked my interest was the Glucocorticoid Receptor. As presented in Jolecule, this protein is in its tertiary structure due to the folding of the protein.This protein is responsible for controlling stress response in the nucleus. The receptor binds to cortisol (cortisol is a steroid hormone that is produced by the adrenal gland) and then travels to the nucleus and binds to the DNA within the nucleus. This process of binding can trigger either two responses; the expression of anti-inflammatory proteins in the nucleus is up regulated or the expression of pro-inflammatory proteins in the cytosol is repressed. Inflammatory proteins are responsible for the healing of tissue when there is an injury present. These proteins can cause redness, heat, and pain at the site of the injury. If the inflammatory proteins persist for too long, the pain at the injury site can become chronic. Glucocorticoids stop this from happening. Because of this, glucocorticoids (as noted by NCBI) are widely used for the suppression of chronic inflammatory diseases such as asthma. Glucoorticoids receptors are also gaining interest within the field of Psychology as these receptors are also responsible for the response of stress in the brain. Psychologists believe that further understanding how the Glucocorticoid Receptor works will help in understanding how psychological diseases develop such as depression.

The Glucocorticoid Receptor is modular in structure. This means that within the receptor, there are different structural parts that have multiple functions. Like all steroid receptors, the Glucocorticoid Receptor has a variable domain, DNA binding domain, hinge region, and hormone binding domain. The variable domain is different for each steroid receptor. For GR, it has the N-terminus which directs the delivery of the protein to the correct organelle. The DNA binding domain controls which gene will be activated when it comes in contact with the DNA within the nucleus. The hinge region is responsible for the movement of the receptors to the nucleus and the hormone binding domain is responsible for the affect of the response of the receptor.

This shows the DNA Binding Domain. This is the only DNA Binding Domain in the Glucocorticoid Receptor 

This is the Hinge Region.

This is the N Terminal 

This is the overall protein

Jube's Fun with Jolecule

                                                                  Antibody Protein 

        I studied the antibody protein. Also known as immunoglobulins, antibodies are specialized cells of the immune system that work to prevent antigens from attacking the body. They work to detect foreign particles and fight it off to defend the body’s immune system. Using jolecule, I was able to see the specific arrangement of an antibody. Antibodies are Y shaped, and they are composed of two antigen binding sites. Each binding site has a heavy chain and a light chain. This variation allows the binding sites to vary from one antibody to the next. The following figures highlight some of the essential aspects of the protein.

           Figure 1: Y Shaped Structure                     

   Figure 2: Constant Region  

Figure 3: Antigen Binding Site

Figure 1 shows the Y shaped structure of the antibody. This structure is beneficial because it can be modified so that the antibody can attach to the specific shape of the protein or sugar molecules attached to the antigen. Furthermore, figure 2 shows the constant region of the structure which functions to communicate with the other proteins in the immune system to determine how to get rid of the antigen. The ends of the heavy (green) chain and light (purple) chain are the constant regions of this structure. In contrast, the tips of the antibody (where the chain labels are in figure 1) represent the antigen binding site as depicted by figure 3. Figure 3 shows an overhead view of where the antigen binds to the chains. When binded, the immune system will be able to attack the antigen to protect the body.

Evidently, all three figures show the tertiary structure of the protein because the light chain and heavy chain are both apparent. To add, the polypeptide chains have folded into their functional shape. As a result, interactions between the chains allow for them to stabilize so that they can function efficiently. Essentially, the presence of both chains contribute to the function of the protein because both chains work together to attach to the antigen present so that it can, ultimately, be destroyed.