| Title: |
Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques. |
| Authors: |
Gillis, RB; Solomon, HV; Govada, L; Oldham, NJ; Dinu, V; Jiwani, SI; Gyasi-Antwi, P; Coffey, F; Meal, A; Morgan, PS; Harding, SE; Helliwell, JR; Chayen, NE; Adams, GG |
| Source: |
1737. |
| Publication Year: |
2020 |
| Collection: |
Imperial College London: Spiral |
| Subject Geographic: |
England |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Sci Rep; http://hdl.handle.net/10044/1/86225 |
| DOI: |
10.1038/s41598-021-81251-2 |
| Availability: |
http://hdl.handle.net/10044/1/86225; https://doi.org/10.1038/s41598-021-81251-2 |
| Rights: |
© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.4D531008 |
| Database: |
BASE |