An abnormal pK(a) value of internal histidine of the insulin molecule revealed by neutron crystallographic analysis

Biochemical and Biophysical Research Communications
Takuya IshikawaNobuo Niimura

Abstract

Insulin is stored in pancreatic beta-cell as hexameric form with Zn2+ ions, while the hormonally active form is monomer. The hexamer requires the coordination of Zn2+ ions to the HisB10. In order to reveal the mechanism of the hexamerization of insulin, we investigated the Zn2+ free insulin at pD6.6 and pD9 by neutron crystallographic analyses. HisB10 is doubly protonated not only at pD6.6 but also at pD9, indicating an abnormal pK(a) of this histidine. It is suggested that HisB10 acts on a strong cation capture and contributes to the high stability of the hexameric form in pancreas.

References

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Nov 14, 1997·Nature Structural Biology·J R Helliwell
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
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Citations

Sep 23, 2009·Acta Crystallographica. Section D, Biological Crystallography·Wakari IwaiNobuo Niimura
Jul 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Jens Luebben, Tim Gruene
Nov 26, 2015·Archives of Biochemistry and Biophysics·William B O'DellFlora Meilleur
Oct 31, 2012·The FEBS Journal·Michael LandrehHans Jörnvall
Feb 7, 2020·Biological Reviews of the Cambridge Philosophical Society·Jacques BaudierGary S Shaw
Feb 20, 2016·Acta Crystallographica. Section D, Structural Biology·Toshiyuki Chatake, Satoru Fujiwara
Apr 20, 2018·Emerging Topics in Life Sciences·Matthew P Blakeley, Alberto D Podjarny

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