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Titre du document / Document title

Role of disulfide bonds in the structure and activity of human insulin

Auteur(s) / Author(s)

CHANG Seung-Gu ; CHOI Ki-Doo ; JANG Seung-Hwan ; SHIN Hang-Cheol ;

Résumé / Abstract

Insulin contains two inter-chain disulfide bonds between the A and B chains (A7-B7 and A20-B19), and one intra-chain linkage in the A chain (A6-A11). To investigate the role of each disulfide bond in the structure, function and stability of the molecule, three des mutants of human insulin, each lacking one of the three disulfide bonds, were prepared by enzymatic conversion of refolded mini-proinsulins. Structural and biological studies of the three des mutants revealed that all three disulfide bonds are essential for the receptor binding activity of insulin, whereas the different disulfide bonds make different contributions to the overall structure of insulin. Deletion of the A20-B19 disulfide bond had the most substantial influence on the structure as indicated by loss of ordered secondary structure, increased susceptibility to proteolysis, and markedly reduced compactness. Deletion of the A6-A11 disulfide bond caused the least perturbation to the structure. In addition, different refolding efficiencies between the three des mutants suggest that the disulfide bonds are formed sequentially in the order A20-B19, A7-B7 and A6-A11 in the folding pathway of proinsulin.

Revue / Journal Title

Molecules and cells    ISSN  1016-8478   CODEN MOCEEK 

Source / Source

2003, vol. 16, no3, pp. 323-330 [8 page(s) (article)]

Langue / Language


Editeur / Publisher

Springer, Singapore, SINGAPOUR  (1990) (Revue)

Localisation / Location

INIST-CNRS, Cote INIST : 26337, 35400011689206.0090

Nº notice refdoc (ud4) : 15516650

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