Sandbox 37
From Proteopedia
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LYSOZYME
Lysozyme, pictured to the right, is an enzyme found commonly in saliva, tears, mucus, and even egg whites. This particular enzyme breaks down bonds of bacterial cell walls. Specifically, lysozyme serves to catalyze the hydrolysis of the Beta (1->4) glycosidic linkage which occurs between N-acetylmuramic acid and N-acetylglucosamine (NAG) of peptidoglycan. Lysozyme is also capable of hydrolyzing polyNAG which constitutes chitin, a major component of fungi cell walls as well as the exoskeletons of insects and crustaceans. [1][2].
The Lysozyme in egg white, specifically hen egg whites (HEW), is the most widely studied and hence the most widely understood species of the enzyme. The picture to the right reveals a HEW lysozyme's cartoon structure with the secondary structure in grey and the yellow being salt bridges throughout the molecule.
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History
Laschtschenko first discovered the acitivty of the enzyme in chicken eggs in 1909. It was not until 1922 when Alexander Fleming stumbled upon accidental observations concerning lysozyme from nasal drippings. He was working in a lab and found that a bacterial plated petri dish which nasal drippings had dripped into resulted in disrupted bacterial activity. He continued by intesively studying the mechanism by which this occurred and found the cleavage sites of lysozyme. Since this time, Lysozyme has become a commercially available enzyme and is even useful in the treatment of ulcers and some bacterial infections. [3].
Mechanism
The mechanism by which lysozyme cleaves beta linkages and be viewed here: Image:Lysozyme-mech.gif]][4].
As is seen here, lysozyme works through a hydrolysis of a glycosidic bond. The fourth sugar which is bound to the lysozyme is put through torsional strain and eventually put into the half chair conformation which greatly weakens the strength of the bond between the fourth and fifth sugars. A proton from Glutamice acid 35 to the Oxygen in the neighboring sugar results in the cleavege of the bond and results in an oxonium ion. Aspartic acid 52 has a carboxylate groups which serves to stablize the ion and acts as a nucleophile to connect to the fourth sugar of the original six sugar chain. Water then attacks the site which results in water being present on the carbon where the bond was originall formed. Glutamine 35 assists in general base catalysis in order to attach the water to the molecule. [5].
Secondary Structure
The secondary structure of lysozyme consists of 5 beta pleated sheets along with 5 alpha helices. These structures are displayed as where the alpha helices are labelled pink and the beta pleated sheets are yellow. The two shortest cartoon rockets which should be yellow beta pleated sheets are labelled pink by the program when told to label different secondary structures differently. This is due to the fact that two of the beta pleated sheets are slightly abnormally shaped and thus can be confused for alpha helices.
Disulfide Bonds
Found throughout the structure of lysozyme are which are labelled yellow and cysteine residues which are labelled blue. Seen here are 8 cysteine residues along with 4 disulfide bonds. The bonds are an integral part of the strucutre and stability of lysozyme.[6].
Hydrogen Bonds
interactions are seen in light blue (the yellow represents the disulfide bonds). Hydrogen bonding occurs between proton donors and acceptors of specific residues. In this way, hydrogen bonds greatly impact the overall structure and stability of the lysozyme molecule as a whole.
Distribution of Polar and NonPolar residues
A distribution of polar vs nonpolar residues can be viewed . The residues on this backbone stucture of lysozyme are labelled blue if they are polar and red if they are nonpolar. By viewing this structure one is capable of seeing the overall dispersion of polar vs. nonpolar residues. Polar residues, which are hydrophillic, are generally found on the outside of a molecule so that they can interact with surrounding water molecules. This is much more apparent when viewing structural format (blue again represents polar while red represents nonpolar residues. Lysozyme is slightly unique in its polar vs nonpolar residues in that, as is apparent in the structure just mentioned, there are still a large number of nonpolar residues towards the outside surface of the molecule. This is due to the fact that lysozyme is a relatively "open" molecule meaning that it is not tightly bound and thus does not hide all of its nonpolar residues with an outward polar residue shell.
Ligand
In biochemistry, a ligand is considered any substance which is able to bind to a biomolecule, in this case an enzyme, and form a complex which serves a biological purpose, in this case the hydrolysis of a glycosidic bond.
The ligand of lysozyme is thus N-acetylmuramic acid and N-acetylglucosamine which bind to the active site of lysozyme very specifically. Lysozyme is only capable of binding polysaccharide chains six sugars in length. The enzyme binds to the fourth sugar and distorts it into a a half chair conformation which results in the glycosidic bond becoming quite weak.
In the binding site of lysozyme are the residues glutamic acid 35 and aspartate 52.
