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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
32
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pubmed:dateCreated |
1993-9-16
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pubmed:abstractText |
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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
17
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8075-82
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:8394123-Chemistry, Physical,
pubmed-meshheading:8394123-Circular Dichroism,
pubmed-meshheading:8394123-Drug Stability,
pubmed-meshheading:8394123-Histidine,
pubmed-meshheading:8394123-Hydrogen Bonding,
pubmed-meshheading:8394123-Hydrogen-Ion Concentration,
pubmed-meshheading:8394123-Insulin,
pubmed-meshheading:8394123-Magnetic Resonance Spectroscopy,
pubmed-meshheading:8394123-Physicochemical Phenomena,
pubmed-meshheading:8394123-Protein Conformation,
pubmed-meshheading:8394123-Protons,
pubmed-meshheading:8394123-Thermodynamics
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pubmed:year |
1993
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pubmed:articleTitle |
Acid stabilization of insulin.
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pubmed:affiliation |
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
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pubmed:publicationType |
Journal Article
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