Lysozymes, 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]
[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[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]
[edit] 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
[edit] 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.
[edit] See also
[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:10.1016/0006-291X(88)90461-5. 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:10.1111/j.1432-1033.1989.tb14857.x. PMID 2546758.
- ^ 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.
- ^ Lönnerdal B (June 2003). "Nutritional and physiologic significance of human milk proteins". Am. J. Clin. Nutr. 77 (6): 1537S–1543S. PMID 12812151.
- ^ Microbiology: A human perspective. Nester, Anderson, Roberts, Nester. 5th Ed. 2007
- ^ Laschtschenko P (1909). "Über die keimtötende und entwicklungshemmende Wirkung Hühnereiweiß" (in German). Z. Hyg. InfektKrankh. 64: 419–427. doi:10.1007/BF02216170.
- ^ 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.
- ^ 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 (4986): 757–61. doi:10.1038/206757a0. 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:10.1038/206761a0. PMID 5840126.
- ^ Johnson, LN (1998). "The early history of lysozme". Nat Struct Mol Biol 5 (11): 942–944. doi:10.1038/2917. PMID 9808036.
- ^ 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.
- ^ Proc R Soc Lond B Bio 167 (1009): 389–401. 1967.
- ^ 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.
[edit] External links
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PDB gallery
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133l: ROLE OF ARG 115 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME. X-RAY STRUCTURE OF HIS 115 AND GLU 115 MUTANTS
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134l: ROLE OF ARG 115 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME. X-RAY STRUCTURE OF HIS 115 AND GLU 115 MUTANTS
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1b5u: CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANT
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1b5v: CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
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1b5w: CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
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1b5x: Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and x-ray analysis of six ser->ala mutants
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1b5y: CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
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1b5z: CONTRIBUTION OF HYDROGEN BONDS TO THE CONFORMATIONAL STABILITY OF HUMAN LYSOZYME: CALORIMETRY AND X-RAY ANALYSIS OF SIX SER->ALA MUTANTS
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1b7l: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7m: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7n: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7o: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7p: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7q: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7r: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1b7s: VERIFICATION OF SPMP USING MUTANT HUMAN LYSOZYMES
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1bb3: HUMAN LYSOZYME MUTANT A96L
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1bb4: HUMAN LYSOZYME DOUBLE MUTANT A96L, W109H
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1bb5: HUMAN LYSOZYME MUTANT A96L COMPLEXED WITH CHITOTRIOSE
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1c43: MUTANT HUMAN LYSOZYME WITH FOREIGN N-TERMINAL RESIDUES
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1c45: MUTANT HUMAN LYSOZYME WITH FOREIGN N-TERMINAL RESIDUES
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1c46: MUTANT HUMAN LYSOZYME WITH FOREIGN N-TERMINAL RESIDUES
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1c7p: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME WITH FOUR EXTRA RESIDUES (EAEA) AT THE N-TERMINAL
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1cj6: T11A MUTANT HUMAN LYSOZYME
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1cj7: T11V MUTANT HUMAN LYSOZYME
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1cj8: T40A MUTANT HUMAN LYSOZYME
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1cj9: T40V MUTANT HUMAN LYSOZYME
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1ckc: T43A MUTANT HUMAN LYSOZYME
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1ckd: T43V MUTANT HUMAN LYSOZYME
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1ckf: T52A MUTANT HUMAN LYSOZYME
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1ckg: T52V MUTANT HUMAN LYSOZYME
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1ckh: T70V MUTANT HUMAN LYSOZYME
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1d6p: HUMAN LYSOZYME L63 MUTANT LABELLED WITH 2',3'-EPOXYPROPYL N,N'-DIACETYLCHITOBIOSE
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1d6q: HUMAN LYSOZYME E102 MUTANT LABELLED WITH 2',3'-EPOXYPROPYL GLYCOSIDE OF N-ACETYLLACTOSAMINE
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1di3: ROLE OF AMINO ACID RESIDUES AT TURNS IN THE CONFORMATIONAL STABILITY AND FOLDING OF HUMAN LYSOZYME
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1di4: ROLE OF AMINO ACID RESIDUES AT TURNS IN THE CONFORMATIONAL STABILITY AND FOLDING OF HUMAN LYSOZYME
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1di5: ROLE OF AMINO ACID RESIDUES AT TURNS IN THE CONFORMATIONAL STABILITY AND FOLDING OF HUMAN LYSOZYME
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1eq4: CRYSTAL STRUCTURES OF SALT BRIDGE MUTANTS OF HUMAN LYSOZYME
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1eq5: CRYSTAL STRUCTURES OF SALT BRIDGE MUTANTS OF HUMAN LYSOZYME
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1eqe: CRYSTAL STRUCTURES OF SALT BRIDGE MUTANTS OF HUMAN LYSOZYME
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1gay: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gaz: Crystal Structure of Mutant Human Lysozyme Substituted at the Surface Positions
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1gb0: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb2: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb3: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb5: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb6: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb7: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb8: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gb9: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gbo: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gbw: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gbx: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gby: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gbz: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gdw: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1gdx: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1ge0: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1ge1: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1ge2: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1ge3: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1ge4: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT LEFT-HANDED HELICAL POSITIONS
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1gev: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gez: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf0: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf3: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf4: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf5: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf6: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf7: BURIED POLAR MUTANT HUMAN LYSOZYME
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1gf8: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gf9: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfa: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfe: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfg: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfh: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfj: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfk: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfr: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gft: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfu: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1gfv: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1hnl: CRYSTAL STRUCTURE OF A GLUTATHIONYLATED HUMAN LYSOZYME: A FOLDING INTERMEDIATE MIMIC IN THE FORMATION OF A DISULFIDE BOND
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1i1z: MUTANT HUMAN LYSOZYME (Q86D)
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1i20: MUTANT HUMAN LYSOZYME (A92D)
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1i22: MUTANT HUMAN LYSOZYME (A83K/Q86D/A92D)
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1inu: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME SUBSTITUTED AT THE SURFACE POSITIONS
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1ioc: CRYSTAL STRUCTURE OF MUTANT HUMAN LYSOZYME, EAEA-I56T
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1ip1: G37A HUMAN LYSOZYME
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1ip2: G48A HUMAN LYSOZYME
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1ip3: G68A HUMAN LYSOZYME
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1ip4: G72A HUMAN LYSOZYME
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1ip5: G105A HUMAN LYSOZYME
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1ip6: G127A HUMAN LYSOZYME
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1ip7: G129A HUMAN LYSOZYME
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1iwt: Crystal Structure Analysis of Human lysozyme at 113K.
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1iwu: Crystal Structure Analysis of Human lysozyme at 127K.
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1iwv: Crystal Structure Analysis of Human lysozyme at 147K.
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1iww: Crystal Structure Analysis of Human lysozyme at 152K.
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1iwx: Crystal Structure Analysis of Human lysozyme at 161K.
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