Lysozyme

Lysozyme is a 14.4 kilodalton enzyme (EC 3.2.1.17) that damages bacterial cell walls by catalyzing hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in a peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrins. It is abundant in a number of secretions, such as tears, saliva, and mucus. Lysozyme is also present in cytoplasmic granules of the polymorphonuclear neutrophils (PMN). Large amounts of lysozyme can be found in egg whites.

Additional recommended knowledge

What is the Correct Way to Check Repeatability in Balances?

Safe Weighing Range Ensures Accurate Results

How to ensure accurate weighing results every day?

Physiology

Most of the bacteria affected by lysozyme are not pathogenic. In some cases, lysozyme is a primary reason these organisms do not become pathogenic. Lysozyme can act to some extent as an innate opsonin, or as an actively lytic enzyme.

Lysozyme serves as a non-specific innate opsonin by binding to the bacterial surface, reducing the negative charge and facilitating phagocytosis of the bacterium before opsonins from the acquired immune system arrive at the scene. In other words, lysozyme makes it easier for phagocytic white blood cells to engulf bacteria.

The enzyme functions by attacking peptidoglycans (found in the cells walls of bacteria, especially Gram-positive bacteria) and hydrolyzing the glycosidic bond that connects N-acetylmuramic acid with the fourth carbon atom of N-acetylglucosamine. It does this by binding to the peptidoglycan molecule in the binding site within the prominent cleft between its two domains. This causes the substrate molecule to adopt a strained conformation similar to that of the transition state. According to Phillips-Mechanism the lysozyme binds to a hexasaccharide. The lysozyme then distorts the 4th sugar in hexasaccharide (the D ring) into a half-chair conformation. In this stressed state the glycosidic bond is easily broken.

The amino acid side chains glutamic acid 35 (Glu35) and aspartate 52 (Asp52) have been found to be critical to the activity of this enzyme. Glu35 acts as a proton donor to the glycosidic bond, cleaving the C-O bond in the substrate, whilst Asp52 acts as a nucleophile to generate a glycosyl enzyme intermediate. The glycosyl enzyme intermediate then reacts with a water molecule, to give the product of hydrolysis and leaving the enzyme unchanged. For further detail see the section on glycoside hydrolases.

Role in disease

In some forms of hereditary amyloidosis, the cause is a mutation in the lysozyme gene, which leads to accumulations of lysozyme in several tissues.^[1]

History

Alexander Fleming (1881-1955), the discoverer of penicillin, described lysozyme in 1922.^[2]

Its structure was described by David Chilton Phillips (1924-1999) in 1965 when he got the first 2 angstrom (200 pm) resolution image.^[3][4] This work led Phillips to provide an explanation for how enzymes speed up a chemical reaction in terms of its physical structures. The original mechanism proposed by Phillips was more recently revised.^[5]

Howard Florey (1898-1968) and Ernst B. Chain (1906-1979) also investigated lysozymes. Although they never made much progress in this field, they developed penicillin, which Fleming had failed to do.

References