Enhanced dynamics of HIV gp120 glycoprotein by small molecule binding.
Biochemistry
; 50(19): 4173-83, 2011 May 17.
Article
em En
| MEDLINE
| ID: mdl-21488663
ABSTRACT
HIV cell entry and infection are driven by binding events to the CD4 and chemokine receptors with associated conformational change of the viral glycoprotein, gp120. Scyllatoxin miniprotein CD4 mimetics and a small molecule inhibitor of CD4 binding, NBD-556, also effectively induce gp120 conformational change. In this study we examine the fluctuation profile of gp120 in context of CD4, a miniprotein mimetic, and NBD-556 with the aim of understanding the effect of ligand binding on gp120 conformational dynamics. Analysis of molecular dynamics trajectories indicate that NBD-556 binding in the Phe 43 cavity enhances the overall mobility of gp120, especially in the outer domain in comparison to CD4 or miniprotein bound complex. Interactions with the more flexible bridging sheet strengthen upon NBD-556 binding and may contribute to gp120 restructuring. The enhanced mobility of D368, E370, and I371 with NBD-556 bound in the Phe 43 cavity suggests that interactions with α3-helix in the outer domain are not optimal, providing further insights into gp120--small molecule interactions that may impact small molecule designs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína gp120 do Envelope de HIV
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos