[en] Lys-70 carboxylation in the active site of class D β lactamases is essential for their activity. Structural, kinetic and affinity studies show that this post-translational modification can be affected by the presence of a poor substrate such as moxalactam but also by the V117T substitution. Val-117 is a strictly conserved hydrophobic residue located in the active site. In addition, inhibition of class D β lactamases by chloride ions is due to a competition between the side chain carboxylate of the modified Lys 70 and chloride ions. Determination of the individual kinetic constants shows that the deacylation of the acyl-enzyme is the rate limiting step for the wild type OXA 10 β lactamase.
Research center :
CIP - Centre d'Ingénierie des Protéines - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vercheval, Lionel ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Di Paolo, Alexandre ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Borel, Franck
Ferrer, Jean-Luc
Sauvage, Eric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Matagne, André ; Université de Liège - ULiège > Département des sciences de la vie > Enzymologie et repliement des protéines
Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Charlier, Paulette ; Université de Liège - ULiège > Département des sciences de la vie > Cristallographie des macromolécules biologiques
Galleni, Moreno ; Université de Liège - ULiège > Département des sciences de la vie > Macromolécules biologiques
Kerff, Frédéric ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Language :
English
Title :
Three factors that modulate the activity of class D β-lactamases and interfere with the post-translational carboxylation of Lys 70
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