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Lysozyme
 
 
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Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s which damage bacterial cell walls by catalyzing hydrolysis
Hydrolysis

Hydrolysis is a chemical reaction during which one or more water are split into hydrogen and hydroxide ions which may go on to participate in further reactions....
 of 1,4-beta-linkages between N-acetylmuramic acid
N-Acetylmuramic acid

N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of Carbon11Hydrogen19NitrogenOxygen8....
 and N-acetyl-D-glucosamine residues in a peptidoglycan
Peptidoglycan

Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall....
 and between N-acetyl-D-glucosamine residues in chitodextrins.






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Lysozyme Crystal1
Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
s which damage bacterial cell walls by catalyzing hydrolysis
Hydrolysis

Hydrolysis is a chemical reaction during which one or more water are split into hydrogen and hydroxide ions which may go on to participate in further reactions....
 of 1,4-beta-linkages between N-acetylmuramic acid
N-Acetylmuramic acid

N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of Carbon11Hydrogen19NitrogenOxygen8....
 and N-acetyl-D-glucosamine residues in a peptidoglycan
Peptidoglycan

Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall....
 and between N-acetyl-D-glucosamine residues in chitodextrins. It is abundant in a number of secretion
Secretion

Secretion is the process of, elaborating and releasing Chemical compound from a cell , or a secreted chemical substance or amount of substance. In contrast to excretion, the substance may have a certain function, rather than being a waste product....
s, such as tears
Tears

Tears are the liquid product of a process of lacrimation to clean and lubricate the eyes. The word lacrimation may also be used in a medical or literary sense to refer to crying....
, saliva
Saliva

Saliva is the watery and usually frothy substance produced in the mouths of humans and most other animals. Saliva is produced in and secreted from the salivary glands....
, and mucus
Mucus

In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. It is a viscous colloid containing antiseptic enzymes and immunoglobulins that serves to protect Epithelium in the respiratory,...
. 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
Alpha-lactalbumin

Lactalbumin, alpha-, also known as LALBA, is a protein which in humans is encoded by the LALBA gene....
 in sequence and structure making them part of the same family.

In humans, the lysozyme enzyme is encoded by the LYZ gene.

Function

The enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
 functions by attacking peptidoglycan
Peptidoglycan

Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall....
s (found in the cells walls of bacteria, especially Gram-positive bacteria) and hydrolyzing
Hydrolysis

Hydrolysis is a chemical reaction during which one or more water are split into hydrogen and hydroxide ions which may go on to participate in further reactions....
 the glycosidic bond that connects N-acetylmuramic acid
N-Acetylmuramic acid

N-Acetylmuramic acid, or MurNAc, is the ether of lactic acid and N-acetylglucosamine with a chemical formula of Carbon11Hydrogen19NitrogenOxygen8....
 with the fourth carbon atom of N-acetylglucosamine
N-Acetylglucosamine

N-Acetylglucosamine is a monosaccharide derivative of glucose. Chemically it is an amide between glucosamine and acetic acid. It has a molecular formula of carbon8hydrogen15nitrogenoxygen6, a molar mass of 221.21 g/mol, and it is significant in several biological systems....
. It does this by binding to the peptidoglycan
Peptidoglycan

Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria, forming the cell wall....
 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 Pseudomonas, when it is deficient 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
Conjunctiva

The conjunctiva is a clear mucous membrane consisting of cells and underlying basement membrane that covers the sclera and lines the inside of the eyelids....
 (membrane covering the eye) is instead protected by secreted enzymes, mainly lysozyme and defensin
Defensin

File:Monomeric and dimeric representations of HBD-2.jpgDefensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates....
. However, when these protective barriers fail, conjunctivitis
Conjunctivitis

Conjunctivitis is an inflammation of the conjunctiva , most commonly due to an allergic reaction or an infection ....
 results.

History

Alexander Fleming
Alexander Fleming

Sir Alexander Fleming was a Scotland biologist and pharmacologist. Fleming published many articles on bacteriology, immunology and chemotherapy....
 (1881-1955), the discoverer of penicillin
Penicillin

Penicillin is a group of antibiotics derived from Penicillium fungi. They are Beta-lactam antibiotics used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms....
, described lysozyme in 1922.

Its structure was described by David Chilton Phillips
David Chilton Phillips

David Chilton Phillips, Baron Phillips of Ellesmere, Order of the British Empire, Fellow of the Royal Society is considered to be a founding father of the now expanding field of structural biology and was an influential figure in science and government....
 (1924-1999) in 1965 when he got the first 2 Ångström
Ångström

An ?ngstr?m or angstrom is an internationally recognized non-SI unit of length equal to 0.1 nanometre or 1 metres. It is sometimes used in expressing the sizes of atoms, lengths of chemical bonds and optical spectrum, and dimensions of parts of integrated circuits....
 (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 along with Fleming developed penicillin.

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