Question

why insulin unable to re-create the disulfide bonds correctly after denaturing?

Answer 1

Proinsulin is a single stranded polypeptide with three intramolecular disulfide bonds.  Insulin is a double stranded polypeptide with two intermolecular disulfide bonds and one intramolecular disulfide bond.  In the case of insulin, you have numerous a and b strands in solution, and the correct a and b cysteine residues must find each other in solution before an intramolecular disulfide bond forms.  Even then, the polypeptide still has high possibility to polymerize.  Proinsulin on the other hand, has only intramolecular disulfide bonds and thus has a high probability of folding in on itself and forming those bonds before forming an intermolecular disulfide bond.

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Answer 2

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