X-ray structure of an unusual Ca sub 2+ site and the roles of Zn sub 2+ and Ca sup 2+ in the assembly, stability, and storage of the insulin hexamer

Journal Article · Tue Jan 29 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00218a006· OSTI ID:5508216

Hill, C P; Dauter, Z; Dodson, E J; Dodson, G G ^[1]; Dunn, M F ^[2]

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1. Univ. of York, Heslington (England)
2. Univ. of California, Riverside (USA)

Metal ion binding to the insulin hexamer has been investigated by crystallographic analysis. Cadmium, lead, and metal-free hexamers have been refined to R values of 0.181, 0.172, and 0.172, against the data of 1.9-, 2.5-, and 2.5-{angstrom} resolution, respectively. These structures have been compared with each other and with the isomorphous two-zinc insulin. The structure of the metal-free hexamer shows that the His(B10) imidazole rings are arranged in a preformed site that binds a water molecule and is poised for Zn{sup 2+} coordination. The structure of the cadmium derivative shows that the binding of Cd{sup 2+} at the center of the hexamer is unusual. There are three symmetry-related sites located within 2.7 {angstrom} of each other, and this position is evidently one-third occupied. It is also shown that the coordinating B13 glutamate side chains of this derivative have two partially occupied conformations. One of these conformations is two-thirds occupied and is very similar to that seen in two-zinc insulin. The other, one-third-occupied conformation, is seen to coordinate the one-third-occupied metal ion. The binding of Ca{sup 2+} to insulin is assumed to be essentially identical with that of Cd{sup 2+}. Thus, the authors conclude that Ca{sup 2+} binding site in the insulin hexamer is unlike that of any other known calcium binding protein. The crystal structures reported herein explain how binding of metal ions stabilizes the insulin hexamer. The role of metal ions in hexamer assembly and dissociation is discussed.

• OSTI ID: 5508216
• Journal Information: Biochemistry; (United States), Vol. 30:4; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
INSULIN
X-RAY DIFFRACTION
CADMIUM COMPOUNDS
CALCIUM COMPOUNDS
CATIONS
CRYSTALLOGRAPHY
MOLECULAR STRUCTURE
ZINC COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
CHARGED PARTICLES
COHERENT SCATTERING
DIFFRACTION
HORMONES
IONS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PROTEINS
SCATTERING
550602* - Medicine- External Radiation in Diagnostics- (1980-)