Lysozyme
"Back in the Spotlight"

by John Geissler and Kathy Thorson

Lysome was discovered in 1922 by Alexander Flemming who also discovered penicillin. A new study published in the March 16, 1999 issue of The Proceedings of the National Academey of Sciences on the potent anit -HIV activity of lysozyme has brought it back into the spotlight. Lysozyme is very prevalent in tears and saliva. Recently researchers at the New York University School of Medicine and U.S. National Institutes of Health (NIH) have found that lysozyme is a potent anti-HIV agent.This helps to explain why HIV is not spread through saliva. During pregnancy, lysozyme is abundantly produced. This may have an advantageous effect on the immune system, to protect against viral and bacterial invasion. Currently researchers are looking at how best to use lysozyme in the war against HIV. These treatments for HIV will probably also be well tolerated by the body, causing few side effects, because they occur naturally.

Little is currently understood abouthe actual inhibition ability of lysozyme on HIV, but a combined effort with ribonuclease is suspected. Thus in the project we will model the binding of lysozyme to hexasaccharide, which is shown below. But first, familiarize yourself with just lysozyme following the instructions supplied.

Mouse Commands

Use the left mouse button to manipulate the screen


Lysozyme has 129 amino acid residues and contains 4 disulfide residues. The enzyme is very compact with a groove for the substrate. It contains three extensive helical regions(residues 5-15, 24-34, 88-96) and two pleated sheet regions(residues 41-45,50-54)

Select cartoon view below to view helical and pleated sheet regions.

Cartoon View

Become familiar with lysozyme!!!!

Check out the hydrogen bonding!

Hydrogen bonds On

Hydrogen bonds Off

MLP Surface

Remove the MLP surface by clicking on reload on from the main menu on Netscape.

Space Filling View

Select space filling view above if you have not done so. Then to see the hydrophobicity of lysozyme, right click on the protein. Then scroll to highlight select, protein, hydrophobic. Then right click again, scroll to select, highlight selection. Now you have displayed the hydrophobic regions of the protein. Polar regions can be found in the same fashion. Simply right click on the protein again, highlight select, protein, polar.

Similarly, the solvent accessible regions can be displayed by right clicking on the protein, highlighting select, hetero and water.

The three dimensional structure of the enzyme with bound (GlcNAc)3 also was determined. Little change( less than 1 Angstrom) in the conformation is exhibited in the enzyme structure with binding.

Hydrogen bonds formed between the enzyme and the saccharide stabilize the binding with help from hydrophobic interactions. There are three sugar binding sites called the ABC sites. labeled in the illustration below. The hexasaccharide (GlcNAc)6 is cleaved between residues 4 and 5, with additional sugar binding sites possible on the enzyme at DEF.

The Active site is readily apparent is a space filling view is used. A major goove is present and is where the binding occurs.

See Figure below

Steric hinderance compromises the normal chain configuration of the D sugar residue.  

 

Quanta Charm was used to produce the following phi/psi plot.

Thank you for visiting and learning about Lysozyme...... watch for it as a new drug in the war against HIV.