Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D-ADP. - Archive ouverte HAL
Article Dans Une Revue Biochemical and Biophysical Research Communications Année : 2008

Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D-ADP.

Andrea Varga
  • Fonction : Auteur
Beáta Flachner
  • Fonction : Auteur
Peter Konarev
  • Fonction : Auteur
Dmitri I. Svergun
  • Fonction : Auteur
Péter Závodszky
  • Fonction : Auteur
Tom Barman
  • Fonction : Auteur
Mária Vas
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00257625 , version 1 (19-02-2008)

Identifiants

Citer

Andrea Varga, Judit Szabó, Beáta Flachner, Béatrice Roy, Peter Konarev, et al.. Interaction of human 3-phosphoglycerate kinase with L-ADP, the mirror image of D-ADP.. Biochemical and Biophysical Research Communications, 2008, 366 (4), pp.994-1000. ⟨10.1016/j.bbrc.2007.12.061⟩. ⟨hal-00257625⟩
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