6GV0

Insulin glulisine

Summary for 6GV0

• Entry DOI: 10.2210/pdb6gv0/pdb
• Descriptor: Insulin, ZINC ION, FORMIC ACID, ... (5 entities in total)
• Functional Keywords: insulin glulisine insulin analogue, hormone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 11888.19

Authors

Chayen, N.E.,Helliwell, J.R.,Solomon-Gamsu, H.V.,Govada, L.,Morgan, M.,Gillis, R.B.,Adams, G. (deposition date: 2018-06-20, release date: 2019-07-03, Last modification date: 2024-11-06)

Primary citation

Gillis, R.B.,Solomon, H.V.,Govada, L.,Oldham, N.J.,Dinu, V.,Jiwani, S.I.,Gyasi-Antwi, P.,Coffey, F.,Meal, A.,Morgan, P.S.,Harding, S.E.,Helliwell, J.R.,Chayen, N.E.,Adams, G.G.
Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques.
Sci Rep, 11:1737-1737, 2021

PubMed Abstract: 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.

PubMed: 33462295
DOI: 10.1038/s41598-021-81251-2

Experimental method

X-RAY DIFFRACTION (1.26 Å)