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

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...

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Detalles Bibliográficos
Autores principales: Fili, S., Valmas, A., Norrman, M., Schluckebier, G., Beckers, D., Degen, T., Wright, J., Fitch, A., Gozzo, F., Giannopoulou, A. E., Karavassili, F., Margiolaki, I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4547821/
https://www.ncbi.nlm.nih.gov/pubmed/26306195
http://dx.doi.org/10.1107/S2052252515013159
Descripción
Sumario: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.