Human insulin polymorphism upon ligand binding and pH variation: the case of 4-ethylresorcinol

IUCrJ

Schluckebier, G.¹  Norrman, M.¹  Fitch, A.²  Wright, J.²  Gozzo, F.³  Beckers, D.⁴  Degen, T.⁴  Valmas, A.⁵  Karavassili, F.⁵  Fili, S.⁵  Giannopoulou, A.E.⁵  Margiolaki, I.⁵ 

[1] Diabetes Protein Engineering, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Malov, Denmark;European Synchrotron Radiation Facility, CS40220, F-38043 Grenoble CEDEX 9, France;Excelsus Structural Solutions, Belgium;PANalytical B.V., Lelyweg 1, 7602 EA Almelo, The Netherlands;Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, GR-26500 Patras, Greece

关键词: POWDER DIFFRACTION;    HUMAN INSULIN;    DIABETES;    SYNCHROTRON RADIATION;    X-RAY DIFFRACTION;    PH VARIATION;    4-ETHYLRESORCINOL;   

DOI  :  10.1107/S2052252515013159

学科分类：数学（综合）

来源: International Union of Crystallography

【 摘 要 】

This study focuses on the effects of the organic ligand 4-ethylresorcinol on the crystal structure of human insulin using powder X-ray crystallography. For this purpose, systematic crystallization experiments have been conducted in the presence of the organic ligand and zinc ions within the pH range 4.50–8.20, while observing crystallization behaviour around the isoelectric point of insulin. High-throughput crystal screening was performed using a laboratory X-ray diffraction system. The most representative samples were selected for synchrotron X-ray diffraction measurements, which took place at the European Synchrotron Radiation Facility (ESRF) and the Swiss Light Source (SLS). Four different crystalline polymorphs have been identified. Among these, two new phases with monoclinic symmetry have been found, which are targets for the future development of microcrystalline insulin drugs.

【 授权许可】

CC BY