Journal article
Structural Stability in the 4-zinc Human Insulin Hexamer
Proceedings of the National Academy of Sciences - PNAS, Vol.81(22), pp.7093-7097
11/01/1984
DOI: 10.1073/pnas.81.22.7093
PMCID: PMC392083
PMID: 6390430
Abstract
X-ray studies on human insulins prepared by semisynthetic and biosynthetic methods have recently been undertaken. Human insulin differs from porcine insulin only at the COOH terminus of the B-chain. The present study reports the crystal structure of 4-zinc human insulin, which is used clinically as a slow-acting preparation. The structure has been refined, using 1.85- angstrom resolution data, to a residual of 0.173. The unit cell is rhombohedral, space group R3, with hexagonal cell constants a = 80.953 and c = 37.636 angstrom, and it is nearly isomorphous with that of 4-zinc porcine insulin. As a result of a conformational change of the first eight residues of the B-chain of molecule 1 from an extended conformation observed in the 2-zinc structure to an α -helical one, the coordination around one of the zinc ions on the 3-fold axis has changed, an additional zinc ion in a general position is bound by the hexamer, and additional hydrogen-bonded interactions help stabilize dimer and hexamer formation. Unlike the surface of the 2-zinc insulin hexamer, which possesses a shallow depression containing a zinc ion and its coordinating water molecules, the 4-zinc human insulin hexamer contains a zinc and chloride ion at the bottom of an 8- angstrom tunnel produced by three parallel α -helices. These α -helices shield the zinc ion from the environment, decreasing the rate of dissociation of the hexamer, and provide an explanation for the slow-acting aspect of the 4-zinc crystalline form.
Details
- Title: Subtitle
- Structural Stability in the 4-zinc Human Insulin Hexamer
- Creators
- G. D. SmithD. C. SwensonE. J. DodsonG. G. DodsonC. D. Reynolds
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.81(22), pp.7093-7097
- Publisher
- National Academy of Sciences of the United States of America
- DOI
- 10.1073/pnas.81.22.7093
- PMID
- 6390430
- PMCID
- PMC392083
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Language
- English
- Date published
- 11/01/1984
- Academic Unit
- Chemistry
- Record Identifier
- 9984622750602771
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