Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques

Sci Rep. 2021 Jan 18;11(1):1737. doi: 10.1038/s41598-021-81251-2.


This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 Å. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 Å with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biophysical Phenomena
  • Crystallography, X-Ray / methods
  • Humans
  • Hypoglycemic Agents / analysis
  • Hypoglycemic Agents / chemistry*
  • Insulin / analogs & derivatives*
  • Insulin / analysis
  • Insulin / chemistry
  • Protein Multimerization
  • Protein Structural Elements
  • Structure-Activity Relationship


  • Hypoglycemic Agents
  • Insulin
  • insulin glulisine