Abstract
SINCE insulin was first shown by Scott1 to crystallize in the presence of zinc ions in 1934, a variety of Zn-containing insulin crystals have been grown2,3. The structures of insulin in the related rhombohedral crystals of 2Zn-insulin and 4Zn-insulin have been solved4,5 and reveal that the molecule is a hexamer, organized as three dimers, each containing a 2-fold symmetry axis and held together by Zn ions. In 2Zn-insulin the hexamer is nearly sym-metrical with the two axial Zn ions and the two molecules of the dimer related closely by a local 2-fold axis. But in 4Zn-insulin the two molecules in the dimer differ remarkably, creating an asymmetric 4Zn-hexamer in which one trimer is essentially equivalent to that in 2Zn-insulin and the other is different by virtue of an additional stretch of N-terminal helix between residues Bl and B8 (refs 6, 7). We report here the structure of a new sym-metrical hexamer, in which all six molecules have the B1–B8 helix seen in 4Zn-insulin. Phenol molecules, found bonding specifi-cally to each molecule, evidently stabilize this new helical conformation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Scott, D. A. Biochem J., Lond. 28, 1592–1602 (1934).
Schlichtkrull, J. in Insulin Crystals (Munksgaard, Copenhagen, 1958).
Baker, E. N. & Dodson, G. G. J. molec Biol. 54, 605–609 (1971).
Adams, M. J. et al. Nature 224, 491–495 (1969).
Bentley, G. A. et al. Nature 261, 166–168 (1976).
Cutfield, J. et al. in Structural Studies on Molecules of Biological Interest (eds Dodson, G. G., Glusker, J. & Sayre, D.) 527–546 (Oxford University Press, 1981).
Chothia, C. et al. Nature 302, 500–505 (1983).
Renscheidt, H. et al. Eur. J. Biochem. 142, 7–14 (1984).
Williamson, K. L. & Williams, R. J. P. Biochemistry 18, 5966–5969 (1979).
Wollmer, A. et al. Biol. Chem., Hoppe-Seyler 368, 903–911 (1987).
Baker, E. N. et al. Phil. Trans. R. Soc. B319, 369–456 (1988).
Konnert & Hendrikson in Computing in Crystallography (eds Diamond, R., Ramasechan, S. & Vanketasan, K.) 1301–1323 (Indian Acad. Sci., Bangalore, 1980).
Agarwal, R. C. Acta crystallogr. A34, 791–809 (1978).
Williams, R. J. P. Carlsberg Res. Commun. 52, 1–30 (1987).
Brange, J. in The Galenics of Insulin (Springer, 1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Derewenda, U., Derewenda, Z., Dodson, E. et al. Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer. Nature 338, 594–596 (1989). https://doi.org/10.1038/338594a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/338594a0
This article is cited by
-
Enhanced hexamerization of insulin via assembly pathway rerouting revealed by single particle studies
Communications Biology (2023)
-
Interaction between phloretin and insulin: a spectroscopic study
Journal of Analytical Science and Technology (2021)
-
Resveratrol as a nontoxic excipient stabilizes insulin in a bioactive hexameric form
Journal of Computer-Aided Molecular Design (2020)
-
Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation
Pharmaceutical Research (2017)
-
Purification and Identification of High Molecular Weight Products Formed During Storage of Neutral Formulation of Human Insulin
Pharmaceutical Research (2015)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.