Crystallization and preliminary crystallographic investigation of a low-pH native insulin monomer with flexible behaviour

Y S Zhang; J L Whittingham; J P Turkenburg; E J Dodson; J Brange; G G Dodson

Crystallization and preliminary crystallographic investigation of a low-pH native insulin monomer with flexible behaviour

Y S Zhang, J L Whittingham, J P Turkenburg, E J Dodson, J Brange, G G Dodson

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Insulin naturally aggregates as dimers and hexamers, whose structures have been extensively analysed by X-ray crystallography. Structural determination of the physiologically relevant insulin monomer, however, is an unusual challenge owing to the difficulty in finding solution conditions in which the concentration of insulin is high enough for crystallization yet the molecule remains monomeric. By utilizing solution conditions known to inhibit insulin assembly, namely 20% acetic acid, crystals of insulin in the monomeric state have been obtained. The crystals are strongly diffracting and a data set extending to 1.6 Angstrom has recently been collected. The crystals nominally belong to the space group I422, with unit-cell parameters a = b = 57.80, c = 54.61 Angstrom, giving rise to one molecule in the asymmetric unit. Preliminary electron-density maps show that whilst most of the insulin monomer is well ordered and similar in conformation to other insulin structures, parts of the B-chain C-terminus main chain adopt more than one conformation.

Original language	English
Pages (from-to)	186-187
Number of pages	2
Journal	Acta crystallographica section d-Biological crystallography
Volume	58
Publication status	Published - Jan 2002

Keywords

RESOLUTION

Cite this

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title = "Crystallization and preliminary crystallographic investigation of a low-pH native insulin monomer with flexible behaviour",

abstract = "Insulin naturally aggregates as dimers and hexamers, whose structures have been extensively analysed by X-ray crystallography. Structural determination of the physiologically relevant insulin monomer, however, is an unusual challenge owing to the difficulty in finding solution conditions in which the concentration of insulin is high enough for crystallization yet the molecule remains monomeric. By utilizing solution conditions known to inhibit insulin assembly, namely 20% acetic acid, crystals of insulin in the monomeric state have been obtained. The crystals are strongly diffracting and a data set extending to 1.6 Angstrom has recently been collected. The crystals nominally belong to the space group I422, with unit-cell parameters a = b = 57.80, c = 54.61 Angstrom, giving rise to one molecule in the asymmetric unit. Preliminary electron-density maps show that whilst most of the insulin monomer is well ordered and similar in conformation to other insulin structures, parts of the B-chain C-terminus main chain adopt more than one conformation.",

keywords = "RESOLUTION",

author = "Zhang, {Y S} and Whittingham, {J L} and Turkenburg, {J P} and Dodson, {E J} and J Brange and Dodson, {G G}",

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month = jan,

language = "English",

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journal = "Acta crystallographica section d-Biological crystallography",

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T1 - Crystallization and preliminary crystallographic investigation of a low-pH native insulin monomer with flexible behaviour

AU - Zhang, Y S

AU - Whittingham, J L

AU - Turkenburg, J P

AU - Dodson, E J

AU - Brange, J

AU - Dodson, G G

PY - 2002/1

Y1 - 2002/1

N2 - Insulin naturally aggregates as dimers and hexamers, whose structures have been extensively analysed by X-ray crystallography. Structural determination of the physiologically relevant insulin monomer, however, is an unusual challenge owing to the difficulty in finding solution conditions in which the concentration of insulin is high enough for crystallization yet the molecule remains monomeric. By utilizing solution conditions known to inhibit insulin assembly, namely 20% acetic acid, crystals of insulin in the monomeric state have been obtained. The crystals are strongly diffracting and a data set extending to 1.6 Angstrom has recently been collected. The crystals nominally belong to the space group I422, with unit-cell parameters a = b = 57.80, c = 54.61 Angstrom, giving rise to one molecule in the asymmetric unit. Preliminary electron-density maps show that whilst most of the insulin monomer is well ordered and similar in conformation to other insulin structures, parts of the B-chain C-terminus main chain adopt more than one conformation.

AB - Insulin naturally aggregates as dimers and hexamers, whose structures have been extensively analysed by X-ray crystallography. Structural determination of the physiologically relevant insulin monomer, however, is an unusual challenge owing to the difficulty in finding solution conditions in which the concentration of insulin is high enough for crystallization yet the molecule remains monomeric. By utilizing solution conditions known to inhibit insulin assembly, namely 20% acetic acid, crystals of insulin in the monomeric state have been obtained. The crystals are strongly diffracting and a data set extending to 1.6 Angstrom has recently been collected. The crystals nominally belong to the space group I422, with unit-cell parameters a = b = 57.80, c = 54.61 Angstrom, giving rise to one molecule in the asymmetric unit. Preliminary electron-density maps show that whilst most of the insulin monomer is well ordered and similar in conformation to other insulin structures, parts of the B-chain C-terminus main chain adopt more than one conformation.

KW - RESOLUTION

M3 - Article

SN - 0907-4449

VL - 58

SP - 186

EP - 187

JO - Acta crystallographica section d-Biological crystallography

JF - Acta crystallographica section d-Biological crystallography

ER -