Zinc–Ligand Interactions Modulate Assembly and Stability of the Insulin Hexamer – A Review

@article{Dunn2005ZincLigandIM,
  title={Zinc–Ligand Interactions Modulate Assembly and Stability of the Insulin Hexamer – A Review},
  author={Michael F Dunn},
  journal={Biometals},
  year={2005},
  volume={18},
  pages={295-303}
}
  • M. Dunn
  • Published 2005
  • Chemistry, Medicine
  • Biometals
Zinc and calcium ions play important roles in the biosynthesis and storage of insulin. Insulin biosynthesis occurs within the β-cells of the pancreas via preproinsulin and proinsulin precursors. In the golgi apparatus, proinsulin is sequestered within Zn2+- and Ca2+-rich storage/secretory vesicles and assembled into a Zn2+ and Ca2+ containing hexameric species, (Zn2+)2(Ca2+)(Proin)6. In the vesicle, (Zn2+)2(Ca2+)(Proin)6 is converted to the insulin hexamer, (Zn2+)2(Ca2+)(In)6, by excision of… Expand
Thermodynamic contributions to the stability of the insulin hexamer.
The insulin hexamer is resistant to degradation and fibrillation, which makes it an important quaternary structure for its in vivo storage in Zn(2+)- and Ca(2+)-rich vesicles in the pancreas and forExpand
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References

SHOWING 1-10 OF 34 REFERENCES
The Glu(B13) carboxylates of the insulin hexamer form a cage for cadmium and calcium ions
: Substitution of Cd2+ for Zn2+ yields a hexameric insulin species containing 3 mol of metal ion per hexamer. The Cd2+ binding loci consist of the two His(B10) sites and a new site involving theExpand
The Glu(B13) carboxylates of the insulin hexamer form a cage for Cd2+ and Ca2+ ions.
TLDR
Insulin solutions to which both Cd2+ and Co2+ have been added in a ratio of 6:2:1 followed by oxidation to the exchange-inert Co3+ state yield stable hybrid species containing both Co3- and Cd1+ with a composition of (In)6(Co3+)2Cd2+. Expand
Comparison of solution structural flexibility and zinc binding domains for insulin, proinsulin, and miniproinsulin.
The chromophoric divalent metal ion chelators 4-(2-pyridylazo)resorcinol (PAR) and 2,2',2"-terpyridine (terpy) are used as kinetic and spectroscopic probes to investigate in solution the SCN-Expand
Mechanisms of stabilization of the insulin hexamer through allosteric ligand interactions.
TLDR
The chromophoric chelator 2,2',2"-terpyridine (terpy) has been used as a kinetic probe of insulin hexamer stability to measure the effect of homotropic and heterotropic effectors on the dissociation kinetics of the Zn2- and Co2-insulin hexamer complexes. Expand
Insulin-metal ion interactions: the binding of divalent cations to insulin hexamers and tetramers and the assembly of insulin hexamers.
TLDR
The kinetics of the assembly of insulin in the presence of limiting metal ion provides strong evidence indicating that the B13 site of the tetramer species can bind Zn2+, Cd2+, or Ca2+ prior to Hexamer formation and that such binding assists hexamer formation. Expand
Characterization of the R-state insulin hexamer and its derivatives. The hexamer is stabilized by heterotropic ligand binding interactions.
TLDR
The relevance of the Co(II)-R6 complexes to carbonic anhydrase catalysis and zinc enzyme model systems is discussed, and UV-visible spectral data and apparent affinity constants for the adducts formed by the Co-II-R6 hexamer with a wide range of anionic ligands are presented. Expand
X-ray Structure of an Unusual Ca 2 + Site and the Roles of Zn 2 + and Ca 2 + in the Assembly , Stability , and Storage of the Insulin Hexamerf
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, againstExpand
The allosteric transition of the insulin hexamer is modulated by homotropic and heterotropic interactions.
TLDR
This work presents the first detailed, quantitative analysis of the ligand-induced T- to R-state allosteric transition of the insulin hexamer, which shows that, in the absence of inorganic anions, the 4-hydroxybenzamide-induced transition is the most cooperative. Expand
Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer
TLDR
The structure of a new sym-metrical hexamer is reported, in which all six molecules have the B1–B8 helix seen in 4Zn-insulin, and Phenol molecules, found bonding specifi-cally to each molecule, evidently stabilize this new helical conformation. Expand
Structural asymmetry and half-site reactivity in the T to R allosteric transition of the insulin hexamer.
TLDR
One- and two-dimensional COSY and NOESY studies show that, in the absence of phenolic compounds, anions act as heterotropic effectors that shift the distribution of hexamer conformations in favor of the R-state with the order of effectiveness, SCN- > N3- >> I- >> Cl-. Expand
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