4-Thiaproline accelerates the slow folding phase of proteins containing cis prolines in the native state by two orders of magnitude.

ABSTRACT: The cis/trans isomerization of peptidyl-prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4-substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4-thiaproline (Thp) has been shown to bias the ring pucker of Pro, to increase the cis population percentage of model peptides in comparison to Pro, and to diminish the activation energy barrier for the cis/trans isomerization reaction. Despite its intriguing properties, Thp has been seldom incorporated into proteins. Moreover, the impact of Thp on the folding kinetics of globular proteins has never been re

SUBMITTER: Loughlin JO 

PROVIDER: S-EPMC10804670 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature