1tby | pdb_00001tby
DISSECTION OF THE FUNCTIONAL ROLE OF STRUCTURAL ELEMENTS OF TYROSINE-63 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME
Structural highlights
Disease[LYSC_HUMAN] Defects in LYZ are a cause of amyloidosis type 8 (AMYL8) [MIM:105200]; also known as systemic non-neuropathic amyloidosis or Ostertag-type amyloidosis. AMYL8 is a hereditary generalized amyloidosis due to deposition of apolipoprotein A1, fibrinogen and lysozyme amyloids. Viscera are particularly affected. There is no involvement of the nervous system. Clinical features include renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash.[1] Function[LYSC_HUMAN] Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe functional role of tyrosine-63 in the catalytic action of human lysozyme (EC 3.2.1.17) has been probed by site-directed mutagenesis. In order to identify the role of Tyr63 in the interaction with substrate, both the three-dimensional structures and the enzymatic functions of the mutants, in which Tyr63 was converted to phenylalanine, tryptophan, leucine, or alanine, have been characterized in comparison with those of the wild-type enzyme. X-ray crystallographical analysis of the mutant enzyme at not less than 1.77-A resolution indicated no remarkable change in tertiary structure except the side chain of 63rd residue. The conversion of Tyr63 to Phe or Trp did not change the enzymatic properties against the noncharged substrate (or substrate analogs) largely, while the conversion to Leu or Ala markedly reduced the catalytic activity to a few percent of wild-type enzyme. Kinetic analysis using p-nitrophenyl penta-N-acetyl-beta-(1----4)-chitopentaoside (PNP-(GlcNAc)5) as a substrate revealed that the reduction of activity should mainly be attributed to the reduction of affinity between enzyme and substrate. The apparent contribution of the phenolic hydroxyl group and the phenol group in the side chain of Tyr63 was estimated to 0.4 +/- 0.4 and 2.5 +/- 0.8 kcal mol-1, respectively. The result suggested that the direct contact between the planar side-chain group of Tyr63 and the sugar residue at subsite B is a major determinant of binding specificity toward a electrostatically neutral substrate in the catalytic action of human lysozyme. Dissection of the functional role of structural elements of tyrosine-63 in the catalytic action of human lysozyme.,Muraki M, Harata K, Jigami Y Biochemistry. 1992 Sep 29;31(38):9212-9. PMID:1390708[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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