Specificity of molecular recognition in oligomerization of bacterial L-asparaginases

Abstract

Bacterial L-asparaginases, which arc widely used in the antitumor therapy, act only as homotctramcrs, because their active sites are located at the interface between the subunits of the enzyme. Since salt bridges substantially stabilize L-asparaginasc tetramcrs, we have supposed that oligomerization of bacterial L-asparaginasc is a high-avidity process. This assumption was proved by bioinformatic and biosensoric methods. It was shown, that a stable tetrameric complex can be formed only by the subunits of the same L-asparaginasc. Using two mutants of L-asparaginase Helicobacter pylori it was shown that specificity of molecular recognition is significantly reduced even by single point mutation at the interface of high-homologous closely-related subunits.