Lysozyme

Lysozyme is a compact globular enzyme with a single polypeptide chain folded into two domains separated by a deep active-site cleft. The hen egg-white lysozyme (HEWL) is the most studied form, consisting of 129 amino acids and four disulfide bonds that stabilize the structure¹.

The catalytic mechanism involves two key residues: glutamic acid 35 (Glu35) and aspartic acid 52 (Asp52). Glu35 acts as a general acid, protonating the glycosidic oxygen, while Asp52 stabilizes the oxocarbenium ion intermediate via electrostatic interactions. This retains the anomeric configuration, classifying lysozyme as a retaining glycosidase².

The enzyme specifically hydrolyzes the β-(1,4) linkage between N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) in peptidoglycan. It can also cleave chitin, a polymer of GlcNAc, albeit less efficiently.

Lysozyme is a key component of the innate immune system, providing protection against bacterial infections, particularly Gram-positive bacteria whose peptidoglycan is exposed. It is present in tears, saliva, mucus, human milk, and phagocytic cells³.

In addition to its antimicrobial role, lysozyme has been implicated in other functions, such as modulation of the immune response and anti-inflammatory properties. It is also used as a food preservative (E1105) and in pharmaceutical preparations.

Beyond animals, lysozyme-like enzymes are found in bacteriophages (e.g., T4 lysozyme) and plants, where they contribute to defense against pathogens.

Lysozyme was discovered by Alexander Fleming in 1922 when he observed that his nasal mucus had antibacterial properties. He named it 'lysozyme' for its ability to lyse bacteria⁴.

In 1965, David Phillips and colleagues at the Royal Institution in London determined the first X-ray crystal structure of hen egg-white lysozyme, providing the first detailed view of an enzyme's active site and mechanism. This work laid the foundation for structural enzymology and structure-based drug design⁵.

Lysozyme is used clinically as a mucolytic agent and in the treatment of infections and inflammatory conditions. It is also incorporated into infant formulas to mimic the protective effects of human milk.

In the food industry, lysozyme is used to prevent late blowing in cheese caused by Clostridium tyrobutyricum, and as a preservative in wines and other products⁶.

Recombinant lysozyme is produced for pharmaceutical use, and research continues into its potential as an anti-cancer agent and in combating antibiotic-resistant bacteria.

Lysozyme has been a model system for studying protein folding, evolution, and enzyme dynamics. Its small size and stability make it ideal for biophysical studies.

One lesser-known fact is that lysozyme can form amyloid fibrils under certain conditions, contributing to systemic amyloidosis in some patients⁷.

Another niche area is the use of lysozyme in the production of protoplasts from bacteria, which are used in genetic engineering.

Additionally, lysozyme from bacteriophage T4 has a different structure and mechanism, and is used as a model for understanding viral enzymes.

In the context of food science, lysozyme is a common allergen in egg white, and its presence must be declared on food labels.

Peptidoglycan

A polymer of sugars and amino acids that forms the bacterial cell wall.

Glycosidic bond

A covalent bond that links a carbohydrate to another group.

X-ray crystallography

A technique used to determine the atomic structure of molecules.

Innate immunity

The non-specific defense mechanisms that come into play immediately or within hours of an antigen's appearance.