Diabetes-associated mutations in insulin identify invariant receptor contacts.

Abstract excerpt

Mutations in human insulin cause an autosomal-dominant syndrome of diabetes and fasting hyperinsulinemia. We demonstrate by residue-specific photo cross-linking that diabetes-associated mutations occur at receptor-binding sites. The studies use para-azido-phenylalanine, introduced at five sites by total protein synthesis. Because two such sites (Val(A3) and Phe(B24)) are largely buried in crystal structures of...

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