Title : Mutational analysis of the absolutely conserved B8Gly: consequence on foldability and activity of insulin.

Pub. Date : 2005 Oct

PMID : 16215634






2 Functional Relationships(s)
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1 In general, replacement of B8Gly by other amino acids causes significant detriment to the foldability of single-chain insulin: the conformations of the three B8 mutants are essentially different from that of wild-type molecules as revealed by circular dichroism; their disulfide stabilities in redox buffer are significantly decreased; their in vitro refolding efficiencies are decreased approximately two folds; the structural stabilities of the mutants with Ser or Thr substitution are decreased significantly, while Leu substitution has little effect as measured by equilibrium guanidine denaturation. Threonine insulin Homo sapiens
2 But Thr or Leu replacement produces significant detriment: the receptor-binding potencies of the two mutants are less than 0.2% of native insulin. Threonine insulin Homo sapiens