The three-dimensional structure of human aurora-C kinase predicted by homology modeling

Aurora-C is a key member of a closely related subgroup of serine/threonine kinase that plays an important role in the completion of essential mitotic events. By means of the homology modeling and the known structure of aurora-B, the 3D structure of aurora-C sourced human sapiens is modeled and then refined by using molecular mechanics (MM) optimization and molecular dynamics (MD) simulation. The final refined model is further assessed by Profile-3D and PROCHECK, which shows that this model is reliable. And then, the inhibitors H-89 and H-8 are docked to aurora-C. The docking study shows that Ala149 and Lys134 are important in inhibition as they form hydrogen bonds and have strong nonbonding interaction with H-89. We also suggest that Ile133, His130, and Ile148 are three important residues in binding as they have strong nonbonding interaction with H-89. The high affinity of H-89 compared with H-8 is explained by the much larger value of van der Waals energy with the enzyme. Our results will be helpful for further experimental investigations.