The role of strong electrostatic interactions at the dimer interface of human glutathione synthetase.
Protein J
; 33(5): 403-9, 2014 Oct.
Article
en En
| MEDLINE
| ID: mdl-25070563
ABSTRACT
The obligate homodimer human glutathione synthetase (hGS) provides an ideal system for exploring the role of protein-protein interactions in the structural stability, activity and allostery of enzymes. The two active sites of hGS, which are 40 Šapart, display allosteric modulation by the substrate γ-glutamylcysteine (γ-GC) during the synthesis of glutathione, a key cellular antioxidant. The two subunits interact at a relatively small dimer interface dominated by electrostatic interactions between S42, R221, and D24. Alanine scans of these sites result in enzymes with decreased activity, altered γ-GC affinity, and decreased thermal stability. Molecular dynamics simulations indicate these mutations disrupt interchain bonding and impact the tertiary structure of hGS. While the ionic hydrogen bonds and salt bridges between S42, R221, and D24 do not mediate allosteric communication in hGS, these interactions have a dramatic impact on the activity and structural stability of the enzyme.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subunidades de Proteína
/
Glutatión Sintasa
Límite:
Humans
Idioma:
En
Revista:
Protein J
Asunto de la revista:
BIOQUIMICA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Estados Unidos