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

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 gluli...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Richard B. Gillis, Hodaya V. Solomon, Lata Govada, Neil J. Oldham, Vlad Dinu, Shahwar Imran Jiwani, Philemon Gyasi-Antwi, Frank Coffey, Andy Meal, Paul S. Morgan, Stephen E. Harding, John R. Helliwell, Naomi E. Chayen, Gary G. Adams
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1baf07d48a3740889f7ac839d941f0d3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1baf07d48a3740889f7ac839d941f0d3
record_format	dspace
spelling	oai:doaj.org-article:1baf07d48a3740889f7ac839d941f0d32021-12-02T10:49:16ZAnalysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques10.1038/s41598-021-81251-22045-2322https://doaj.org/article/1baf07d48a3740889f7ac839d941f0d32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81251-2https://doaj.org/toc/2045-2322Abstract 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.Richard B. GillisHodaya V. SolomonLata GovadaNeil J. OldhamVlad DinuShahwar Imran JiwaniPhilemon Gyasi-AntwiFrank CoffeyAndy MealPaul S. MorganStephen E. HardingJohn R. HelliwellNaomi E. ChayenGary G. AdamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Richard B. Gillis Hodaya V. Solomon Lata Govada Neil J. Oldham Vlad Dinu Shahwar Imran Jiwani Philemon Gyasi-Antwi Frank Coffey Andy Meal Paul S. Morgan Stephen E. Harding John R. Helliwell Naomi E. Chayen Gary G. Adams Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
description	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.
format	article
author	Richard B. Gillis Hodaya V. Solomon Lata Govada Neil J. Oldham Vlad Dinu Shahwar Imran Jiwani Philemon Gyasi-Antwi Frank Coffey Andy Meal Paul S. Morgan Stephen E. Harding John R. Helliwell Naomi E. Chayen Gary G. Adams
author_facet	Richard B. Gillis Hodaya V. Solomon Lata Govada Neil J. Oldham Vlad Dinu Shahwar Imran Jiwani Philemon Gyasi-Antwi Frank Coffey Andy Meal Paul S. Morgan Stephen E. Harding John R. Helliwell Naomi E. Chayen Gary G. Adams
author_sort	Richard B. Gillis
title	Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
title_short	Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
title_full	Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
title_fullStr	Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
title_full_unstemmed	Analysis of insulin glulisine at the molecular level by X-ray crystallography and biophysical techniques
title_sort	analysis of insulin glulisine at the molecular level by x-ray crystallography and biophysical techniques
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1baf07d48a3740889f7ac839d941f0d3
work_keys_str_mv	AT richardbgillis analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT hodayavsolomon analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT latagovada analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT neiljoldham analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT vladdinu analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT shahwarimranjiwani analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT philemongyasiantwi analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT frankcoffey analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT andymeal analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT paulsmorgan analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT stepheneharding analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT johnrhelliwell analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT naomiechayen analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques AT garygadams analysisofinsulinglulisineatthemolecularlevelbyxraycrystallographyandbiophysicaltechniques
_version_	1718396574193680384

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

Ejemplares similares