Lysozyme

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lysozyme
Identifiers
Symbol	LYZ
HUGO	6740
Entrez	4069
OMIM	153450
RefSeq	NM_000239
UniProt	P61626
Other data
EC number	3.2.1.17
Locus	Chr. 12 [1]

Lysozyme (BE: lysosyme) is a 14.4 kilodalton enzyme (EC 3.2.1.17), commonly referred to as the "body's own antibiotic" since it kills bacteria. Lysozyme is a an enzyme that destroys bacterial cell walls by hydrolyzing the polysaccharide component of the cell wall.^[1] It is abundantly present in a number of secretions, such as tears. This protein is present in cytoplasmic granules of the polymorphonuclear neutrophils (PMN) and released through the mucosal secretions (such as tears and saliva). They can also be found in high concentration in egg white.

Contents 1 Physiology 2 Role in disease 3 Diagnostic use 4 History 5 References

[edit] 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 bond that connects N-acetyl muramic 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 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.

[edit] Role in disease

In some forms of hereditary amyloid, the cause is a mutation in the lysozyme gene, which leads to accumulated lysozyme in several tissues.^[2]

[edit] Diagnostic use

Lysozyme levels in the blood are often increased in sarcoidosis. Levels are considered raised at 8 mg/l or above.The predictive value for raised ACE level and lysozyme raised level (in combination), for sarcoidosis is up to 83%.

[edit] History

Alexander Fleming (1881-1955), the discoverer of penicillin, described lysozyme in 1922.^[3]

Its structure was described by David Chilton Phillips (1924-1999) in 1965 when he got the first 2 angstrom (200 pm) resolution image.^[4][5] 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.^[6]

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.

[edit] References