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Structure and comparison of the motor domain of centromere‐associated protein E
Author(s) -
Shibuya Asuka,
Ogo Naohisa,
Sawada Jun-ichi,
Asai Akira,
Yokoyama Hideshi
Publication year - 2021
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798321000176
Subject(s) - kinesin , motor protein , atpase , mitosis , centromere , microbiology and biotechnology , regulator , function (biology) , biophysics , biology , protein structure , chemistry , microtubule , biochemistry , enzyme , gene , chromosome
Centromere‐associated protein E (CENP‐E) plays an essential role in mitosis and is a target candidate for anticancer drugs. However, it is difficult to design small‐molecule inhibitors of CENP‐E kinesin motor ATPase activity owing to a lack of structural information on the CENP‐E motor domain in complex with its inhibitors. Here, the CENP‐E motor domain was crystallized in the presence of an ATP‐competitive inhibitor and the crystal structure was determined at 1.9 Å resolution. In the determined structure, ADP was observed instead of the inhibitor in the nucleotide‐binding site, even though no ADP was added during protein preparation. Structural comparison with the structures of previously reported CENP‐E and those of other kinesins indicates that the determined structure is nearly identical except for several loop regions. However, the retention of ADP in the nucleotide‐binding site of the structure strengthens the biochemical view that the release of ADP is a rate‐limiting step in the ATPase cycle of CENP‐E. These results will contribute to the development of anticancer drugs targeting CENP‐E and to understanding the function of kinesin motor domains.