An abnormal pK{sub a} value of internal histidine of the insulin molecule revealed by neutron crystallographic analysis

Journal Article · Fri Nov 07 00:00:00 EST 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.08.071· OSTI ID:21146673

Ishikawa, Takuya; Chatake, Toshiyuki; Morimoto, Yukio ^[1]; Maeda, Mitsuru; Kurihara, Kazuo ^[2]; Tanaka, Ichiro ^[3]; Niimura, Nobuo ^[4]

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1. Kyoto University Research Reactor, Asashironishi 2, Kumatori, Osaka 590-0494 (Japan)
2. Neutron Structural Biology, Japan Atomic Energy Agency, Shirakata-shirane, 2-4, Tokai, Ibaraki 319-1195 (Japan)
3. Faculty of Engineering, Ibaraki University, Naka-Narusawa, 4-12-1, Hitachi, Ibaraki 316-8511 (Japan)
4. Frontier Research Center for Applied Atomic Sciences, Ibaraki University, Naka-Narusawa, 4-12-1, Hitachi, Ibaraki 316-8511 (Japan)

Insulin is stored in pancreatic {beta}-cell as hexameric form with Zn{sup 2+} ions, while the hormonally active form is monomer. The hexamer requires the coordination of Zn{sup 2+} ions to the HisB10. In order to reveal the mechanism of the hexamerization of insulin, we investigated the Zn{sup 2+} 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{sub 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.

• OSTI ID: 21146673
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 376, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2008.08.071; PII: S0006-291X(08)01583-0; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CATIONS
CRYSTALLOGRAPHY
HISTIDINE
INSULIN
MOLECULES
MONOMERS
NEUTRONS
PANCREAS
POLYMERIZATION
ZINC IONS