Possible Role of B8Gly in Insulin Structural Motif

ZHANG Hong, TANG Yue-Hua, FENG You-Min*
( State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences, Shanghai 200031, China )

Abstract    In the insulin structural motif n1-Cys-Gly-X10-Cys-n2-Cys-Cys-X3-Cys-X8-Cys-n3, there are seven absolutely conserved amino acid residues, and the only Gly is at position B8. When B8Gly was substituted with Ala by means of site-directed mutagenesis, a mutant insulin, [B8Ala]human insulin was obtained. The receptor binding capacity and in vivo biological activity of the [B8Ala]human insulin were about 2.5% and 10% of native porcine insulin, respectively. The far-UV circular dichroism (CD) spectra of [B8Ala]human insulin and human insulin showed that the relative content of ¦Á-helix in the mutant somewhat decreased . The results indicate that the B8Gly in the insulin structural motif is unreplaceble.
Key words    insulin structural motif
£» insulin mutant£» [B8Ala]human insulin

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