An allosteric mode of inhibition is characterized by the competitor binding at a separate site from that of the "substrate-ligand", and showing similar affinity for the target regardless of the presence of the substrate-ligand. Analysis of the crystal structures reported for Aurora-A in the presence of TACC3 and N-Myc offers a rationale for the allosteric inhibition. Numerous, conformational changes in the protein upon binding each substrate are observed (Fig. ). The N-lobe sheets β1-β3 and helices HB-HC show a significant deviation in their relative positions between both structures, and the deviation appears to be conformationally transmitted to αG helix in the C-lobe, which is directly involved in N-Myc binding. The displacement in β1-β3 and helices αB-αC in the TACC3/Aur-A structure, when compared to that of N-Myc, was also observed in a recently reported CEP192/Aurora-A structure (Notably, binding of CEP192 to the TACC3 site on Aurora-A stimulates kinase activity, consistent with a conserved function through a similar allosteric mechanism). 52