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Structures of human and bovine chloro-, bromo- and iodo- insulin derivatives

Insulin is a small protein hormone synthesized in humans and other mammals within the beta cells of the islets of Langerhans in the pancreas. It consists of two polypeptide chains linked by two sulfur bridges. When crystals of native insulin are grown in high chloride ion concentration the rhombohedral 4-Zn insulin is obtained while 2-Zn insulin forms in low chloride ion concentration1, 2. Crystals of the human chloro-derivative were known to have a phase transition upon cooling, resulting in doubling of the c-axis3, 4. Different coordination spheres of the zinc atom have been described for the room temperature and low temperature structures. In the present study we were interested to see the influence of high bromide and iodide concentrations on the structure of insulin and on the coordination sphere of the zinc ion. We were also interested to get more insight into the phase transition that occurs upon cooling. Data were collected to high resolution (from 1.2 to 1.6 Å for different data sets) at synchrotrons ELETTRA in Trieste (single crystal diffraction data at 100 K) and ESRF in Grenoble (powder diffraction data of the human bromo-derivative at room temperature). All of the investigated insulin derivatives belong to the R3 space group. Now we have obtained also cryo-cooled crystals of the chloro-derivative with no phase transition. The bromo-insulin structure that is also of the 4-Zn type. The Zn ion situated on the three-fold axis is tetrahedrally coordinated (3 His and Br) while the off-axial is tetrahedrally coordinated (2 His and 2 Br). On contrary, the iodo-derivative is of the 2-Zn type but with a disordered tetrahedrally (3His and I) and octahedrally coordinated zinc atom (3 His and 3 H2O).

insulin derivatives; crystal structure

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