Crystal structure of desheptapeptide(B24-B30)insulin at 1.6 A resolution: implications for receptor binding

Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):2975-80. doi: 10.1073/pnas.94.7.2975.

Abstract

The crystal structure of desheptapeptide (B24-B30) insulin (DHPI), a virtually inactive analog of insulin, was determined at 1.6 A resolution. In the refined structure model, DHPI retains three alpha-helices (A1-A8, A12-A18, and B9-B19) as its structural framework, while great conformational changes occur in the N and C termini of B-chain. The beta-turn, which lies in B20-B30 in insulin and insulin analogs with high potency, no longer exists in DHPI. Relative motion is observed among the three alpha-helices, each as a rigid functional group. In contrast, a region covering B5-B6 and A6-A11 exhibits a relatively stable conformation. We interpret our results as identifying: (i) the importance of beta-turn in determining the receptor-binding potency of insulin and (ii) a leading role of PheB24 in maintaining the beta-turn structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Insulin / analogs & derivatives*
  • Insulin / chemistry
  • Insulin / metabolism
  • Models, Chemical
  • Molecular Sequence Data
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Protein Binding

Substances

  • Insulin
  • Peptide Fragments
  • insulin, des(heptapeptide)(B24-B30)-

Associated data

  • PDB/1DE1