The conformational stability and flexibility of insulin with an additional intramolecular cross-link.
J Biol Chem
; 266(3): 1611-5, 1991 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-1988440
ABSTRACT
The conformational stability and flexibility of insulin containing a cross-link between the alpha-amino group of the A-chain to the epsilon-amino group of Lys29 of the B-chain was examined. The cross-link varied in length from 2 to 12 carbon atoms. The conformational stability was determined by guanidine hydrochloride-induced equilibrium denaturation and flexibility was assessed by H2O/D2O amide exchange. The cross-link has substantial effects on both conformational stability and flexibility which depend on its length. In general, the addition of a cross-link enhances conformational stability and decreases flexibility. The optimal length for enhanced stability and decreased flexibility was the 6-carbon link. For the 6-carbon link the Gibbs free energy of unfolding was 8.0 kcal/mol compared to 4.5 kcal/mol for insulin, and the amide exchange rate decreased by at least 3-fold. A very short cross-link (i.e. the 2-carbon link) caused conformational strain that was detectable by a lack of stabilization in the Gibbs free energy of unfolding and enhancement in the amide exchange rate compared to insulin. The effect of the cross-link length on insulin hydrodynamic properties is discussed relative to previously obtained receptor binding results.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insulina
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
1991
Tipo de documento:
Article