A distal point mutation in the streptavidin-biotin complex preserves structure but diminishes binding affinity: experimental evidence of electronic polarization effects?
Biochemistry
; 49(22): 4568-70, 2010 Jun 08.
Article
em En
| MEDLINE
| ID: mdl-20462252
ABSTRACT
We have identified a distal point mutation in streptavidin that causes a 1000-fold reduction in biotin binding affinity without disrupting the equilibrium complex structure. The F130L mutation creates a small cavity occupied by a water molecule; however, all neighboring side chain positions are preserved, and protein-biotin hydrogen bonds are unperturbed. Molecular dynamics simulations reveal a reduced mobility of biotin binding residues but no observable destabilization of protein-ligand interactions. Our combined structural and computational studies suggest that the additional water molecule may affect binding affinity through an electronic polarization effect that impacts the highly cooperative hydrogen bonding network in the biotin binding pocket.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Biotina
/
Mutação Puntual
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Estreptavidina
/
Elétrons
/
Simulação de Dinâmica Molecular
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos