Lysozyme

Lysozyme is a family of enzymes which damage 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. C-type lysozymes are closely related to alpha-lactalbumin in sequence and structure making them part of the same family.

Physiology

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.

Role in disease

Lysozyme is part of the innate immune system. Children fed infant formula lack lysozyme in their diet and have three times the rate of diarrheal disease. Since Lysozyme is a natural form of protection from pathogens like Salmonella, E.Coli and Pseudemonas, when it is difficient due to infant formula feeding, can lead to increased incidence of disease.

Whereas the skin is a protective barrier due to its dryness and acidity, the conjunctiva (membrane covering the eye) is instead protected by secreted enzymes, mainly lysozyme and defensin. However when these protective barriers fail, conjunctivitis results.

History

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

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

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

External links

• Ventria Bioscience provides a non-animal source of breastmilk equivalent lysozyme
• InVitria sells recombinant human lysozyme
• The Lysozyme Protein
• Lysozyme structure and related articles