Prediction and validation of the three-dimensional structure of glucokinase-1 from Phytophthora infestans

According to its primary structure, the [PITG_06016] gene encodes for one of the 7 glucokinases present in Phytophthora infestans ( Pi GlcK-1), the causal agent of late blight disease. Currently, there are no structural studies of any of its enzymes, being the determination of the three-dimensional (3D) structure of Pi GlcK-1 a necessary contribution in the deduction of its functions, its interaction with ligands, and possible regulatory mechanisms. In this work we present the first structural model obtained by in silico tools for Pi GlcK-1. For the prediction of this model, different algorithms were used to find the best annealing, refinement, and qualitative evaluation of them. A structural comparison of the predicted model with other structures of crystallized kinase enzymes allowed us to identify the regions of interaction with their classical substrates (glucose and ATP), as well as to identify the amino acid residues involved in the binding of other substrates such as fructose and ADP. In addition, we propose a possible recognition region of PPi, an activator of kinase activity that includes the GXGE motif, conserved in enzymes of the ribokinase (RK) family, which distinguishes this Pi GlcK-1 from a classical glucokinase. Accordingly, these findings suggest PPi-binding motif as potential targets for the development of inhibitors of Pi GlcK-1 activity.