New Factors Enhancing the Reactivity of Cysteines in Molten Globule-Like Structures
| Autor: | Giada Cattani, Giorgia Gambardella, Alessio Bocedi, Giorgio Ricci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Protein Folding
Protein Conformation chymotrypsinogen Chymotrypsinogen Article Catalysis Inorganic Chemistry Hydrophobic effect molten globule lcsh:Chemistry bovine serum albumin chemical kinetics hydrophobic interaction Reactivity (chemistry) Cysteine Disulfides Settore BIO/10 Physical and Theoretical Chemistry Bovine serum albumin lysozyme Molecular Biology lcsh:QH301-705.5 Spectroscopy chemistry.chemical_classification biology Chemistry oxidative folding cysteine reactivity transient complex ribonuclease Hydrogen-Ion Concentration Kinetics Muramidase Oxidation-Reduction Oxidative folding Organic Chemistry General Medicine Molten globule Computer Science Applications lcsh:Biology (General) lcsh:QD1-999 Reagent biology.protein Biophysics Thiol |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 6949, p 6949 (2020) International Journal of Molecular Sciences Volume 21 Issue 18 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Protein cysteines often play crucial functional and structural roles, so they are emerging targets to design covalent thiol ligands that are able to modulate enzyme or protein functions. Some of these residues, especially those involved in enzyme mechanisms&mdash including nucleophilic and reductive catalysis and thiol-disulfide exchange&mdash display unusual hyper-reactivity such a property is expected to result from a low pKa and from a great accessibility to a given reagent. New findings and previous evidence clearly indicate that pKa perturbations can only produce two&ndash four-times increased reactivity at physiological pH values, far from the hundred and even thousand-times kinetic enhancements observed for some protein cysteines. The data from the molten globule-like structures of ribonuclease, lysozyme, bovine serum albumin and chymotrypsinogen identified new speeding agents, i.e., hydrophobic/electrostatic interactions and productive complex formations involving the protein and thiol reagent, which were able to confer exceptional reactivity to structural cysteines which were only intended to form disulfides. This study, for the first time, evaluates quantitatively the different contributions of pKa and other factors to the overall reactivity. These findings may help to clarify the mechanisms that allow a rapid disulfide formation during the oxidative folding of many proteins. |
| Databáze: | OpenAIRE |
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