Additional disulfide bonds in insulin: Prediction, recombinant expression, receptor binding affinity, and stability.

ABSTRACT: The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. The N-terminus of insulin's B-chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had to be increased in many instances and single X-ray structures as well as structures from MD simulations had to be used. The analogues that were identified by the algorithm without extensive adjustmen

SUBMITTER: Vinther TN 

PROVIDER: S-EPMC4420526 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature