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Phenol-promoted structural transformation of insulin in solution
A Wollmer1, B Rannefeld, B R Johansen
1Abteilung Physiologische Chemie, Rheinisch-Westfälische Technische Hochschule Aachen.
Biological Chemistry Hoppe-Seyler
|August 1, 1987
Summary
Phenolic additives like m-cresol induce structural changes in insulin, promoting helix formation and a 2 Zn to 4 Zn transition. This highlights insulin
Area of Science:
- Biochemistry
- Structural Biology
- Pharmaceutical Science
Background:
- Phenolic additives are crucial for preserving insulin preparations.
- These additives can significantly alter insulin's three-dimensional structure in solution.
Purpose of the Study:
- To investigate the conformational effects of phenolic additives on insulin.
- To elucidate the mechanism by which m-cresol influences insulin structure and transitions.
Main Methods:
- Circular Dichroism (CD) spectroscopy was used to monitor conformational changes.
- Experiments involved various insulin forms (monomeric, dimeric, crystalline) and metal ions (Zn2, Ni2).
- Crystallographic analysis of insulin grown in the presence of m-cresol.
Main Results:
- m-Cresol increased helical content in insulin, similar to halide ions, indicating a 2 Zn to 4 Zn insulin transition.
- This effect was dependent on the presence of Zn2 and absent in monomeric insulin.
- m-Cresol disrupted 2 Zn insulin crystals but promoted the formation of monoclinic crystals with 4 Zn hexamers.
Conclusions:
- m-Cresol induces a structural transition in insulin mirroring the 2 Zn to 4 Zn transformation.
- The study confirms a strong correlation between insulin's solution and crystal structures.
- Insulin exhibits significant structural plasticity influenced by its environment and additives.