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

GILLIS, RB, SOLOMON, HV, GOVADA, L, OLDHAM, NJ, DINU, V, JIWANI, SI, GYASI-ANTWI, P, COFFEY, F, MEAL, A, MORGAN, PS, HARDING, Stephen E., HELLIWELL, John R., CHAYEN, Naomi E. and ADAMS, Gary G. (2021). Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques. Scientific reports, 11: 1737.

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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.

Item Type: Article
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SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 03 May 2023 08:59
Last Modified: 11 Oct 2023 15:15

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