Lysozyme

Lysozyme
Lysozyme single crystal
Identifiers
EC number	3.2.1.17
CAS number	9001-63-2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles

Lysozyme
PDB rendering based on 132l.
Available structures PDB 133L, 134L, 1B5U, 1B5V, 1B5W, 1B5X, 1B5Y, 1B5Z, 1B7L, 1B7M, 1B7N, 1B7O, 1B7P, 1B7Q, 1B7R, 1B7S, 1BB3, 1BB4, 1BB5, 1C43, 1C45, 1C46, 1C7P, 1CJ6, 1CJ7, 1CJ8, 1CJ9, 1CKC, 1CKD, 1CKF, 1CKG, 1CKH, 1D6P, 1D6Q, 1DI3, 1DI4, 1DI5, 1EQ4, 1EQ5, 1EQE, 1GAY, 1GAZ, 1GB0, 1GB2, 1GB3, 1GB5, 1GB6, 1GB7, 1GB8, 1GB9, 1GBO, 1GBW, 1GBX, 1GBY, 1GBZ, 1GDW, 1GDX, 1GE0, 1GE1, 1GE2, 1GE3, 1GE4, 1GEV, 1GEZ, 1GF0, 1GF3, 1GF4, 1GF5, 1GF6, 1GF7, 1GF8, 1GF9, 1GFA, 1GFE, 1GFG, 1GFH, 1GFJ, 1GFK, 1GFR, 1GFT, 1GFU, 1GFV, 1HNL, 1I1Z, 1I20, 1I22, 1INU, 1IOC, 1IP1, 1IP2, 1IP3, 1IP4, 1IP5, 1IP6, 1IP7, 1IWT, 1IWU, 1IWV, 1IWW, 1IWX, 1IWY, 1IWZ, 1IX0, 1IY3, 1IY4, 1JKA, 1JKB, 1JKC, 1JKD, 1JSF, 1JWR, 1LAA, 1LHH, 1LHI, 1LHJ, 1LHK, 1LHL, 1LHM, 1LMT, 1LOZ, 1LYY, 1LZ1, 1LZ4, 1LZ5, 1LZ6, 1LZR, 1LZS, 1OP9, 1OUA, 1OUB, 1OUC, 1OUD, 1OUE, 1OUF, 1OUG, 1OUH, 1OUI, 1OUJ, 1QSW, 1RE2, 1REM, 1REX, 1REY, 1REZ, 1TAY, 1TBY, 1TCY, 1TDY, 1UBZ, 1W08, 1WQM, 1WQN, 1WQO, 1WQP, 1WQQ, 1WQR, 1YAM, 1YAN, 1YAO, 1YAP, 1YAQ, 207L, 208L, 2BQA, 2BQB, 2BQC, 2BQD, 2BQE, 2BQF, 2BQG, 2BQH, 2BQI, 2BQJ, 2BQK, 2BQL, 2BQM, 2BQN, 2BQO, 2HEA, 2HEB, 2HEC, 2HED, 2HEE, 2HEF, 2LHM, 2MEA, 2MEB, 2MEC, 2MED, 2MEE, 2MEF, 2MEG, 2MEH, 2MEI, 2NWD, 2ZIJ, 2ZIK, 2ZIL, 2ZWB, 3EBA, 3FE0, 3LHM
Identifiers
Symbols	LYZ;
External IDs	OMIM: 153450 MGI: 96897 HomoloGene: 121490 GeneCards: LYZ Gene
EC number	3.2.1.17
Gene Ontology Molecular function • lysozyme activity • protein binding • hydrolase activity, acting on glycosyl bonds Cellular component • extracellular region • extracellular space Biological process • inflammatory response • cell wall macromolecule catabolic process • cytolysis • defense response to bacterium Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4069	17105
Ensembl	ENSG00000090382	ENSMUSG00000069516
UniProt	P61626	Q3TXG2
RefSeq (mRNA)	NM_000239.2	NM_017372
RefSeq (protein)	NP_000230.1	NP_059068
Location (UCSC)	Chr 12: 69.74 – 69.75 Mb	Chr 10: 116.68 – 116.69 Mb
PubMed search	[1]	[2]

Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase, are glycoside hydrolases, enzymes (EC 3.2.1.17) 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 (PMN). 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.^[1][2]

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^{[citation needed]}. According to Phillips-Mechanism, the lysozyme binds to a hexasaccharide. The lysozyme then distorts the fourth 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, 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.^{[citation needed]}

Further information: glycoside hydrolase

Role in disease

Lysozyme is part of the innate immune system. Reduced lysozyme levels have been associated with bronchopulmonary dysplasia in newborns.^[3] Children fed infant formula lacking lysozyme in their diet have three times the rate of diarrheal disease.^[4] Since lysozyme is a natural form of protection from gram-positive pathogens like Bacillus and Streptococcus,^[5] 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 (membrane covering the eye) is, instead, protected by secreted enzymes, mainly lysozyme and defensin. However, when these protective barriers fail, conjunctivitis results.

In certain cancers (especially myelomonocytic leukemia) 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,^[6] although it was not until 1922 that the name 'lysozyme' was coined, by Alexander Fleming (1881–1955), the discoverer of penicillin.^[7] Fleming first observed the antibacterial action of lysozyme when he treated bacterial cultures with nasal mucus from a patient suffering from a head cold.^[7]

The three-dimensional structure of hen egg white lysozyme was described by David Chilton Phillips (1924–1999) in 1965, when he obtained the first 2-Ångström (200 pm) resolution model via X-ray crystallography.^[8][9] The structure was publicly presented at a Royal Institution lecture in 1965.^[10] 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.^[11] 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.^[12] 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.^[13]

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.

See also

• Egg allergy

References

1. ^ 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:10.1016/0006-291X(88)90461-5. PMID 2829884. 
2. ^ 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:10.1111/j.1432-1033.1989.tb14857.x. PMID 2546758. 
3. ^ Revenis ME, Kaliner MA (August 1992). "Lactoferrin and lysozyme deficiency in airway secretions: association with the development of bronchopulmonary dysplasia". J. Pediatr. 121 (2): 262–70. doi:10.1016/S0022-3476(05)81201-6. PMID 1640295. 
4. ^ Lönnerdal B (June 2003). "Nutritional and physiologic significance of human milk proteins". Am. J. Clin. Nutr. 77 (6): 1537S–1543S. PMID 12812151. 
5. ^ Microbiology: A human perspective. Nester, Anderson, Roberts, Nester. 5th Ed. 2007
6. ^ Laschtschenko P (1909). "Über die keimtötende und entwicklungshemmende Wirkung Hühnereiweiß" (in German). Z. Hyg. InfektKrankh. 64: 419–427. doi:10.1007/BF02216170. 
7. ^ ^{a b} Fleming A (1 May 1922). "On a remarkable bacteriolytic element found in tissues and secretions". Proc Roy Soc Ser B 93 (653): 306–317. doi:10.1098/rspb.1922.0023. http://www.jstor.org/pss/80959. 
8. ^ 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:10.1038/206757a0. PMID 5891407. 
9. ^ 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:10.1038/206761a0. PMID 5840126. 
10. ^ Johnson, LN (1998). "The early history of lysozme". Nat Struct Mol Biol 5 (11): 942–944. doi:10.1038/2917. PMID 9808036. 
11. ^ Canfield, RE (1963). "The Amino Acid Sequence of Egg White Lysozyme". J Biol Chem 238 (8): 2698–2707. PMID 14063294. http://www.jbc.org/content/238/8/2698.short. 
12. ^ Proc R Soc Lond B Bio 167 (1009): 389–401. 1967. 
13. ^ 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:10.1038/35090602. PMID 11518970. 

External links

• MeSH Muramidase
• "Lysozyme: enzyme, sequence, crystallization, structure". lysozyme.co.uk. http://lysozyme.co.uk/. Retrieved 2009-01-04. 
• Proteopedia.org HEW Lysozyme