Lysozyme
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Lysozymes, also known as muramidase or N-acetylmuramide glycanhydrolase, are a family of enzymes (EC 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 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.
In humans, the lysozyme enzyme is encoded by the LYZ gene.[1][2]
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[edit] Function
The enzyme functions by attacking peptidoglycans (found in the cell 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.
[edit] 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.[citation needed] 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 (membrane covering the eye) is instead protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results.
[edit] History
Alexander Fleming (1881-1955), the discoverer of penicillin, described lysozyme in 1922.[3]
Its structure was described by David Chilton Phillips (1924-1999) in 1965 when he got the first 2 Ångström (200 pm) resolution image.[4][5] 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.[6]
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.
[edit] References
- ^ Yoshimura K, Toibana A, Nakahama K (January 1988). "Human lysozyme: sequencing of a cDNA, and expression and secretion by Saccharomyces cerevisiae". Biochem. Biophys. Res. Commun. 150 (2): 794–801. doi:. PMID 2829884.
- ^ Peters CW, Kruse U, Pollwein R, Grzeschik KH, Sippel AE (July 1989). "The human lysozyme gene. Sequence organization and chromosomal localization". Eur. J. Biochem. 182 (3): 507–16. doi:. PMID 2546758.
- ^ Fleming A (May 1922). "On a remarkable bacteriolytic element found in tissues and secretions". Proc Roy Soc Ser B 93 (653): 306-317. http://www.jstor.org/pss/80959.
- ^ Blake CC, Koenig DF, Mair GA, North AC, Phillips DC, Sarma VR. (1965). "Structure of hen egg-white lysozyme. A three-dimensional Fourier synthesis at 2 Angstrom resolution". Nature 206 (986): 757-61. doi:. PMID 5891407.
- ^ Johnson LN, Phillips DC. (1965). "Structure of some crystalline lysozyme-inhibitor complexes determined by X-ray analysis at 6 Angstrom resolution". Nature 206 (986): 761-3. doi:. PMID 5840126.
- ^ Vocadlo DJ, Davies GJ, Laine R, Withers SG. (2001). "Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate". Nature 412 (6849): 835-8. doi:. PMID 11518970.
[edit] See also
[edit] External links
- MeSH Muramidase
- "Lysozyme: enzyme, sequence, crystallization, structure". lysozyme.co.uk. http://lysozyme.co.uk/. Retrieved on 2009-01-04.
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