A model of insulin fibrils derived from the x-ray crystal structure of a monomeric insulin (despentapeptide insulin)

Proteins. 1997 Apr;27(4):507-16.

Abstract

The crystal structure of despentapeptide insulin, a monomeric insulin, has been refined at 1.3 A spacing and subsequently used to predict and model the organization in the insulin fibril. The model makes use of the contacts in the densely packed despentapeptide insulin crystal, and takes into account other experimental evidence, including binding studies with Congo red. The dimensions of this model fibril correspond well with those measured experimentally, and the monomer-monomer contacts within the fibril are in accordance with the known physical chemistry of insulin fibrils. Using this model, it may be possible to predict mutations in insulin that might alleviate problems associated with fibril formation during insulin therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Crystallography, X-Ray
  • Insulin / analogs & derivatives*
  • Insulin / chemistry*
  • Models, Molecular
  • Protein Structure, Secondary*
  • Protein Structure, Tertiary*
  • Water / analysis

Substances

  • Insulin
  • Water
  • insulin, despentapeptide(B26-B30)-