1tby
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DISSECTION OF THE FUNCTIONAL ROLE OF STRUCTURAL ELEMENTS OF TYROSINE-63 IN THE CATALYTIC ACTION OF HUMAN LYSOZYME
OverviewOverview
The 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.
DiseaseDisease
Known diseases associated with this structure: Amyloidosis, renal OMIM:[153450], Microphthalmia, syndromic 1 OMIM:[309800]
About this StructureAbout this Structure
1TBY is a Single protein structure of sequence from Homo sapiens. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.
ReferenceReference
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
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