Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases.
These are enzymes that 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.
Lysozyme is abundant in a number of secretions, such as tears, saliva, human milk, and mucus.
It is also present in cytoplasmic granules of the polymorphonuclear neutrophils.
Large amounts of lysozyme can be found in egg white.
C-type lysozymes are closely related to alpha-lactalbumin 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 functions by attacking peptidoglycans
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 fourth sugar in hexasaccharide into a half-chair conformation.
In this stressed state, the glycosidic bond is easily broken.
The amino acid side-chains glutamic acid 35 and aspartate 52 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,
whereas 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.
Reduced lysozyme levels have been associated with bronchopulmonary dysplasia in newborns.
Children fed infant formula lacking lysozyme in their diet have three times the rate of
diarrheal disease.
Since lysozyme is a natural form of protection from gram-positive pathogens like Bacillus
and Streptococcus, a deficiency 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
is, instead, protected by secreted enzymes, mainly lysozyme and defensin.
However, when these protective barriers fail, conjunctivitis results.
In certain cancers excessive production of lysozyme by cancer cells can lead to toxic
levels of lysozyme in the blood.
High lysozyme blood levels can lead to kidney failure and low blood potassium, conditions
that may improve or resolve with treatment of the primary malignancy.
History The antibacterial property of hen egg white,
due to the lysozyme it contains, was first observed by Laschtschenko in 1909, although
it was not until 1922 that the name 'lysozyme' was coined, by Alexander Fleming, the discoverer
of penicillin.
Fleming first observed the antibacterial action of lysozyme when he treated bacterial cultures
with nasal mucus from a patient suffering from a head cold.
The three-dimensional structure of hen egg white lysozyme was described by David Chilton
Phillips in 1965, when he obtained the first 2-ångström resolution model via X-ray crystallography.
The structure was publicly presented at a Royal Institution lecture in 1965.
Lysozyme was the second protein structure and the first enzyme structure to be solved
via X-ray diffraction methods, and the first enzyme to be fully sequenced that contains
all twenty common amino acids.
As a result of Phillips' elucidation of the structure of lysozyme, it was also the first
enzyme to have a detailed, specific mechanism suggested for its method of catalytic action.
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.
Chemical synthesis The first chemical synthesis of a lysozyme
protein was attempted by Prof. George W. Kenner and his group at the University of Liverpool
in England.
This was finally achieved in 2007 by Steve Kent at the University of Chicago who made
synthetic functional lysozyme molecule.
See also Egg allergy
References
External links Muramidase at the US National Library of Medicine
Medical Subject Headings "Lysozyme: enzyme, sequence, crystallization,
structure".
lysozyme.co.uk.
Retrieved 2009-01-04.
Proteopedia.org HEW Lysozyme JBdirectory: Lysozyme chloride