Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D-ADP.
Biochem Biophys Res Commun
; 366(4): 994-1000, 2008 Feb 22.
Article
em En
| MEDLINE
| ID: mdl-18096512
ABSTRACT
l-Nucleoside-analogues, mirror images of the natural d-nucleosides, are a new class of antiviral and anticancer agents. In the cell they have to be phosphorylated to pharmacologically active triphosphate forms, the last step seems to involve human 3-phosphoglycerate kinase (hPGK). Here we present a steady state kinetic and biophysical study of the interaction of the model compound l-MgADP with hPGK. l-MgADP is a good substrate with k(cat) and K(m) values of 685s(-1) and 0.27mM, respectively. Double inhibition studies suggest that l-MgADP binds to the specific adenosine-binding site and protects the conformation of hPGK molecule against heat denaturation, as detected by microcalorimetry. Structural details of the interaction in the enzyme active site are different for the d- and l-enantiomers (e.g. the effect of Mg(2+)), but these differences do not prevent the occurrence of the catalytic cycle, which is accompanied by the hinge-bending domain closure, as indicated by SAXS measurements.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoglicerato Quinase
/
Difosfato de Adenosina
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Hungria