Evaluation of conformational changes in diabetes-associated mutation in insulin a chain: a molecular dynamics study.

ABSTRACT: Insulin plays a central role in the regulation of metabolism in humans. Mutations in the insulin gene can impair the folding of its precursor protein, proinsulin, and cause permanent neonatal-onset diabetes mellitus known as Mutant INS-gene induced Diabetes of Youth (MIDY) with insulin deficiency. To gain insights into the molecular basis of this diabetes-associated mutation, we perform molecular dynamics simulations in wild-type and mutant (Cys(A7) to Tyr or C(A7)Y) insulin A chain in aqueous solutions. The C(A7)Y mutation is one of the identified mutations that impairs the protein folding by substituting the cysteine residue which is required for the disulfide bond formation. A comparative analysis reveals structural differences between the wild-type and the mutant conformations. The ana

SUBMITTER: Kim YH 

PROVIDER: S-EPMC4382306 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature