Effect of genetic circular permutation near the active site on the activity and stability of an enzyme inhibitor
| Autor: | Ronald T. Piervincenzi, Ashutosh Chilkoti |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Protein Denaturation
Protein Folding Stereochemistry Protein Conformation Swine Bioengineering Protein Engineering Structure-Activity Relationship Protein structure Enzyme Stability Structure–activity relationship Animals Binding site Enzyme Inhibitors Molecular Biology Pancreas chemistry.chemical_classification Binding Sites biology Chemistry Active site Isothermal titration calorimetry Circular permutation in proteins Recombinant Proteins Amino acid Enzyme Activation Mutation biology.protein Protein folding DNA Circular alpha-Amylases Peptides Biotechnology Protein Binding |
| Zdroj: | Biomolecular engineering. 21(1) |
| ISSN: | 1389-0344 |
| Popis: | We report here the effect of circular permutation on the structure and function of a model protein tendamistat, a 74 amino acid competitive inhibitor of porcine pancreatic alpha-amylase. The activity and stability of wild type and two permuted tendamistat variants were characterized by measurement of alpha-amylase kinetic and thermodynamic binding parameters and their thermodynamics of unfolding. Our results show that large variations in structure and function can occur upon circularly permuting tendamistat near its active site that are not obvious, a priori, from the structure of the native protein and we propose a structural thermodynamic explanation of the experimental observations. |
| Databáze: | OpenAIRE |
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