Lysozyme
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2008-07-08T00:34:42Z
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[[Image:lysozyme crystal1.JPG|thumb|200px|Lysozyme single crystal.]]
'''Lysozyme''' is a family of [[enzyme]]s ({{EC number|3.2.1.17}}) 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 [[secretion]]s, such as [[tears]], [[saliva]], and [[mucus]]. Lysozyme is also present in [[cytoplasmic]] granules of the [[polymorphonuclear neutrophil]]s (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==
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, lysozyme makes it easier for phagocytic [[white blood cells]] to engulf bacteria.
The [[enzyme]] functions by attacking [[peptidoglycan]]s (found in the cells walls of bacteria, especially [[Gram-positive bacteria]]) and [[hydrolysis|hydrolyzing]] the glycosidic bond that connects [[N-Acetylmuramic acid|''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.
<br />{{further|[[glycoside hydrolase]]}}
==Role in disease==
In some forms of [[amyloidosis|hereditary amyloidosis]], the cause is a [[mutation]] in the lysozyme [[gene]], which leads to accumulations of lysozyme in several [[biological tissue|tissues]].<ref>{{OMIM|105200}}</ref>
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]].<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 [[picometer|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.
==References==
<div class="references-small"><references/></div>
==External links==
* [http://macromoleculeinsights.com/lysozyme.php The Lysozyme Protein]
* [http://lysozyme.co.uk/ Lysozyme structure and related articles]
{{Glycoside hydrolases}}
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