Comparison of the dynamics of an engineered insulin monomer and dimer by acid-quenched amide proton exchange. Non-local stabilization of interchain hydrogen bonds by dimerization.
J Mol Biol
; 230(2): 387-94, 1993 Mar 20.
Article
en En
| MEDLINE
| ID: mdl-8464054
Dynamic differences between an engineered insulin monomer and dimer are investigated under physiological conditions by an adaptation of the method of acid-quenched amide proton exchange. Although exchange lifetimes of amide protons involved in intrachain hydrogen bonds are similar in the two analogs, dimerization specifically stabilizes two interchain hydrogen bonds (LeuB6-NH...O = C-CysA6 and CysA11-NH...O = C-GluB4) that are distant from the dimer interface. Such non-local stabilization demonstrates that fluctuations in the tertiary structure of the monomer are damped by dimerization. As the B6-A6 and A11-B4 hydrogen bonds are specific to the crystallographic T-state, their stabilization also indicates that the R-state (an allosteric feature of hexamer assembly) is not significantly populated in an isolated dimer. Our results are discussed in reference to recent hypotheses that crystal structures of insulin depict inactive conformers and that detachment of interchain contacts accompany receptor binding.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estructura Secundaria de Proteína
/
Insulina
Idioma:
En
Revista:
J Mol Biol
Año:
1993
Tipo del documento:
Article
Pais de publicación:
Países Bajos