Chemical, Target, and Bioactive Properties of Allosteric Modulation
Figure 1
The concept of multiple binding sites on a single protein visualized schematically (A) and in protein data bank structure 1JSU (B).
The ATP binding site was shown in green on cyclin dependent kinase 2 (CDK2) (grey), commonly referred to as the orthosteric binding site. One allosteric binding site (type V inhibitors) was shown in red, closely located to the orthosteric binding site. Also shown was a non-allosteric inhibitor (green, projected from PDB 1HCK) and an allosteric inhibitor (red, projected from PDB 3PY1). Finally cyclin-A was visualized pairing (light grey) with CDK2 and the natural inhibitor CDKN1B (dark green) to show the potential of allosteric inhibitors to disrupt the CDK2- cyclin-A protein-protein interaction.