Lysozyme

From Wikipedia, the free encyclopedia

lysozyme
Identifiers
Symbol(s)	LYZ
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 an enzyme (EC 3.2.1.17), commonly referred to as the "body's own antibiotic" since it kills bacteria. 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.

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, lysosyme 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. 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 (Mendelian Inheritance in Man (OMIM) 105200).

[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.<ref>Fleming A. On a remarkable bacteriolytic element found in tissues and secretions. Proc Roy Soc Ser B 1922;93:306-17</ref>

Its structure was described by David Chilton Phillips (1924-1999) in 1965 when he got the first 2 angstrom (200 pm) resolution image.<ref>Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR. Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Ångstrom resolution. Nature, 206, 757-61</ref><ref>Johnson LN, Phillips DC. Structure of some crystalline lysozyme-inhibitor complexes determined by X-ray analysis at 6 Ångstrom resolution. Nature, 206, 761-3.</ref> 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.<ref>Vocadlo, D. J.; Davies, G. J.; Laine, R.; Withers, S. G. Nature 2001, 412, 835.</ref>

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.