Abstract
The native core structure of hirudin, a thrombin specific inhibitor, contains 24 hydrogen bonds, two stretches of β-sheet and three disulfide bonds. Hirudin unfolds in the presence of denaturant and thiol catalyst by shuffling its native disulfide bonds and converting to scrambled structures that consist of 11 identified isomers. The composition of scrambled isomers, which characterizes the structure of denatured hirudin, varies as a function of denaturing conditions. The unfolding pathway of hirudin has been constructed by quantitative analysis of scrambled isomers unfolded under increasing concentrations of various denaturants. The results demonstrate a progressive expansion of the polypeptide chain and the existence of a structurally defined stable intermediate along the pathway of unfolding.
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Bulychev, A., Chang, JY. Unfolding of Hirudin Characterized by the Composition of Denatured Scrambled Isomers. J Protein Chem 18, 771–778 (1999). https://doi.org/10.1023/A:1020681518265
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DOI: https://doi.org/10.1023/A:1020681518265