1di5
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ROLE OF AMINO ACID RESIDUES AT TURNS IN THE CONFORMATIONAL STABILITY AND FOLDING OF HUMAN LYSOZYME
OverviewOverview
To clarify the role of amino acid residues at turns in the conformational, stability and folding of a globular protein, six mutant human lysozymes, deleted or substituted at turn structures were investigated by, calorimetry, GuHCl denaturation experiments, and X-ray crystal analysis., The thermodynamic properties of the mutant and wild-type human lysozymes, were compared and discussed on the basis of their three-dimensional, structures. For the deletion mutants, Delta47-48 and Delta101, the deleted, residues are in turns on the surface and are absent in human, alpha-lactalbumin, which is homologous to human lysozyme in amino acid, sequence and tertiary structure. The stability of both mutants would be, expected to increase due to a decrease in conformational entropy in the, denatured state; however, both proteins were destabilized. The, destabilizations were mainly caused by the disappearance of intramolecular, hydrogen bonds. Each part deleted was recovered by the turn region like, the alpha-lactalbumin structure, but there were differences in the, main-chain conformation of the turn between each deletion mutant and, alpha-lactalbumin even if the loop length was the same. For the point, mutants, R50G, Q58G, H78G, and G37Q, the main-chain conformations of these, substitution residues located in turns adopt a left-handed helical region, in the wild-type structure. It is thought that the left-handed non-Gly, residue has unfavorable conformational energy compared to the left-handed, Gly residue. Q58G was stabilized, but the others had little effect on the, stability. The structural analysis revealed that the turns could rearrange, the main-chain conformation to accommodate the left-handed non-Gly, residues. The present results indicate that turn structures are able to, change their main-chain conformations, depending upon the side-chain, features of amino acid residues on the turns. Furthermore, stopped-flow, GuHCl denaturation experiments on the six mutants were performed. The, effects of mutations on unfolding-refolding kinetics were significantly, different among the mutant proteins. The deletion/substitutions in turns, located in the alpha-domain of human lysozyme affected the refolding rate, indicating the contribution of turn structures to the folding of a, globular protein.
DiseaseDisease
Known diseases associated with this structure: Amyloidosis, renal OMIM:[153450], Microphthalmia, syndromic 1 OMIM:[309800]
About this StructureAbout this Structure
1DI5 is a Single protein structure of sequence from Homo sapiens with NA as ligand. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.
ReferenceReference
Role of amino acid residues at turns in the conformational stability and folding of human lysozyme., Takano K, Yamagata Y, Yutani K, Biochemistry. 2000 Jul 25;39(29):8655-65. PMID:10913274
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