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The structure of T3R3 bovine insulin
Structural highlights
FunctionINS_BOVIN Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. Publication Abstract from PubMedThe crystal structures of three conformations, T(6), T(3)R(3) and R(6), of bovine insulin were solved at 1.40, 1.30 and 1.80 A resolution, respectively. All conformations crystallized in space group R3. In contrast to the T(6) and T(3)R(3) structures, different conformations of the N-terminal B-chain residue PheB1 were observed in the R(6) insulin structure, resulting in an eightfold doubling of the unit-cell volume upon cooling. The zinc coordination in each conformation was studied by X-ray absorption spectroscopy (XAS), including both EXAFS and XANES. Zinc adopts a tetrahedral coordination in all R(3) sites and an octahedral coordination in T(3) sites. The coordination distances were refined from XAS with a standard deviation of <0.01 A. In contrast to the distances determined from the medium-resolution crystal structures, the XAS results were in good agreement with similar coordination geometries found in small molecules, as well as in other high-resolution insulin structures. As the radiation dose for XRD experiments is two orders of magnitude higher compared with that of XAS experiments, the single crystals were exposed to a higher degree of radiation damage that affected the zinc coordination in the T(3) sites in particular. Furthermore, XANES spectra for the zinc sites in T(6) and R(6) insulin were successfully calculated using finite difference methods and the bond distances and angles were optimized from a quantitative XANES analysis. The structures of T(6), T(3)R(3) and R(6) bovine insulin: combining X-ray diffraction and absorption spectroscopy.,Frankaer CG, Knudsen MV, Noren K, Nazarenko E, Stahl K, Harris P Acta Crystallogr D Biol Crystallogr. 2012 Oct;68(Pt 10):1259-71. Epub 2012 Sep, 13. PMID:22993080[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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