Molecular dynamics simulations of human glutathione transferase P1-1: conformational fluctuations of the apo-structure.
Proteins
; 37(1): 10-9, 1999 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-10451546
We have investigated by molecular dynamics simulations the conformational fluctuations of the monomer of human apo-glutathione transferase P1-1. After attainment of steady-state dynamics, the structural fluctuations involve mainly the protein segments that participate also in the holo-apo transition discussed in the accompanying article (Stella et al., 1999:37:1-9.). The most mobile region is the C-terminal segment of helix 2. In contrast, helices 1, 6, 7, and 8 constitute a relatively rigid protein core. An "essential dynamics" analysis of the simulation shows that the largest fluctuations involve specific regions of glutathione transferases. In such regions, atomic motions are correlated. Motions of helix 2 are accounted for by the second most prominent principal component, which reveals a fluctuation between two distinct conformations. The residues that constitute the H-site undergo a breathing motion, possibly relevant during the binding of hydrophobic cosubstrates. Based on our simulation, several experimental findings can be rationalized, including the viscosity-dependent reactivity of Cys 47 and Cys 101 as well as the selective proteolysis of the peptide bond between Lys 44 and Ala 45. We have also modeled the structural changes that lead to the formation of an intrachain disulfide bridge between cysteines 47 and 101 and to the inactivation of the enzyme. The resulting structure maintains essentially the native fold except for helix 2, which closes the G-site. Proteins 1999;37:10-19.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Apoproteínas
/
Conformación Proteica
/
Simulación por Computador
/
Modelos Moleculares
/
Glutatión
/
Glutatión Transferasa
/
Isoenzimas
/
Modelos Químicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Proteins
Asunto de la revista:
BIOQUIMICA
Año:
1999
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos