Structure and comparison of the motor domain of centromere-associated protein E.
Acta Crystallogr D Struct Biol
; 77(Pt 3): 280-287, 2021 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-33645531
ABSTRACT
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 1.9â
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Cromossômicas não Histona
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article