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Structure of the new crystal form of the T6 human nickel insulin derivative

Insulin is structured as a two polypeptide chains (chain A consists of 21 and chain B of 30 amino acids) linked by two sulfur bridges. Insulin is used medically in Type 1 diabetes mellitus. There are three forms of insulin hexamers named T6, T3Rf3 and R6. These notations refer to the folding of the N-terminal part of the B chains (residue B1-B8) in insulin hexamers. It has been shown that chloride ions induce the T to R transitions at residue B4-B8 in three molecules out of six in the insulin hexamer forming the T3Rf3 hexamer. As a part of our ongoing research on the crystallization and structural studies on human insulin derivatives in the present study the zinc ions in insulin were substituted with nickel and crystallized in high chloride concentration. Crystals of a new form of the human Ni-insulin derivative were grown by the hanging drop vapour diffusion method using Zn-free insulin. The single crystal diffraction data were collected at the ELETTRA Synchrotron Light Laboratory, beam line XRD-1, to 1.52 Å resolution. The investigated insulin derivative belongs to the R3 space group (hexagonal setting) with cell parameters a = b = 45.78 Å, c = 116.90 Å,  = 120°. There are two nickel ions in the hexamer, coordinated octahedrally by three histidines and three water molecules. Coordination around nickel atom showing the electron density is shown on Figure 1. The coordination of nickel ions are similar as in the previously reported form, however the packing of the hexamers in the unit cell is quite different. Coordination of nickel ions and conformation of the insulin molecule will be discussed.

nickel insulin derivative; X-ray; hexamer

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