Hydrophilic Thr can replace the hydrophobic and absolutely conservative A3Val in insulin

Abstract A mutant insulin, [A3Thr]human insulin, was obtained by means of site-directed mutagenesis. The [A3Thr]human insulin retains 50% receptor-binding potency and nearly total in vivo biological activity compared with native insulin, and can be crystallized using the same condition of native insulin. The results demonstrate that the absolutely conservative and hydrophobic valine at A3 can be substituted by hydrophilic threonine.