New Factors Enhancing the Reactivity of Cysteines in Molten Globule-Like Structures.
Int J Mol Sci
; 21(18)2020 Sep 22.
Article
in En
| MEDLINE
| ID: mdl-32971812
ABSTRACT
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-including nucleophilic and reductive catalysis and thiol-disulfide exchange-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-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Muramidase
/
Protein Folding
/
Cysteine
/
Disulfides
Type of study:
Prognostic_studies
Language:
En
Journal:
Int J Mol Sci
Year:
2020
Document type:
Article
Affiliation country: