Acid stabilization of insulin
| Autor: | Alita Miller, Steven R. Maple, Allen H. Pekar, Donald B. Spencer, David N. Brems, Christopher Bryant, Diane Lee Bakaysa, Karen S. McCune |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Circular dichroism
Conformational change Magnetic Resonance Spectroscopy Chemical Phenomena Protein Conformation Stereochemistry medicine.medical_treatment Protonation Biochemistry Protein structure Drug Stability medicine Insulin Histidine chemistry.chemical_classification Chemistry Physical Circular Dichroism Hydrogen Bonding Hydrogen-Ion Concentration Amino acid chemistry Thermodynamics Chemical stability Protons |
| Zdroj: | Biochemistry. 32:8075-8082 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00083a004 |
| Popis: | The effect of pH on the conformational stability of insulin was studied. Surprisingly, the Gibbs free energy of unfolding increased approximately 30% by acidification. pH titration of insulin's conformational stability is described by a transition involving a single proton with an apparent pK(a) of 7.0. The acid stabilization of insulin's conformation was attributed to the protonation of histidine at position 5 on the B-chain (HB5) as determined by 1H-NMR of the histidines, selective amino acid alteration, and enthalpies of ionization. Further acidification (at least to pH 2) does not decrease the free energy of unfolding. A conformational change in the tertiary structure, as indicated by the near-UV circular dichroism spectrum, accompanies this change in stability. We propose that this acid stabilization of insulin is physiologically important in maintaining insulin stability in the acid environment of the secretory/storage granules of the beta-cell of the pancreatic islets of Langerhans. |
| Databáze: | OpenAIRE |
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