Modeling the Interaction of the UxuR–ExuR Heterodimer with the Components of the Metabolic Pathway of Escherichia col i for Hexuronate Utilization

The UxuR transcription factor is a repressor of a number of hexuronate catabolism genes. It can form heterodimers with its ExuR paralog, which in the presence of glucuronate leads to the activation of repressed by UxuR genes. Previously, it was predicted by the method of flexible sequential molecular docking that sugars bind to the inter-domain linkers of UxuR and ExuR, affecting the mutual arrangement of protein domains. Similar calculations on the models of the UxuR–ExuR heterodimer corresponding to the four points of its molecular dynamic simulation also predict the binding of sugars with inter-domain linkers. Changes in the protein conformation modulate the place and degree of affinity of such an interaction. A hypothesis is proposed about the appearance of more stable UxuR–ExuR–glucuronate complexes, which have increased binding affinity with some conformations of inter-domain linkers of proteins. This reduces the number of free monomers, and hence, of UxuR homodimers in the presence of these sugars, and reduces the repression by UxuR of its regulon.