Crystal structure of the motor domain of centromere‐associated protein E in complex with a non‐hydrolysable ATP analogue

Abstract

Centromere-associated protein E (CENP-E) is a kinesin motor protein essential for mitosis and a new target for anticancer agents with less side effects. To rationally design anticancer drug candidates based on structure, it is important to determine the three-dimensional structure of the CENP-E motor domain bound to its inhibitor. Here, we report the first crystal structure of the CENP-E motor domain in complex with a non-hydrolysable ATP analogue, adenylyl-imidodiphosphate (AMPPNP). Furthermore, the structure is compared with the ADP-bound form of the CENP-E motor domain as well as the AMPPNP-bound forms of other kinesins. This study indicates that helix a4 of CENP-E participates in the slow binding of CENP-E to microtubules. These results will contribute to the development of anticancer drugs targeting CENP-E.

Kinesin-7 CENP-E in tumorigenesis: Chromosome instability, spindle assembly checkpoint, and applications

“…A recent study has revealed the crystal structure of CENP-E motor domain in complex with AMPPNP. And the helix α4 is required for the slow binding of CENP-E to microtubules (Shibuya et al, 2023). In the future, crystal structures of CENP-E in complex with specific inhibitors will help to elucidate the mechanisms of kinesin motors and the development of anticancer drugs.…”