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Binding patterns of inhibitors to different pockets of kinesin Eg5.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2024 Jun; Vol. 756, pp. 109998. Date of Electronic Publication: 2024 Apr 18. - Publication Year :
- 2024
-
Abstract
- The kinesin-5 family member, Eg5, plays very important role in the mitosis. As a mitotic protein, Eg5 is the target of various mitotic inhibitors. There are two targeting pockets in the motor domain of Eg5, which locates in the α2/L5/α3 region and the α4/α6 region respectively. We investigated the interactions between the different inhibitors and the two binding pockets of Eg5 by using all-atom molecular dynamics method. Combined the conformational analysis with the free-energy calculation, the binding patterns of inhibitors to the two binding pockets are shown. The α2/L5/α3 pocket can be divided into 4 regions. The structures and binding conformations of inhibitors in region 1 and 2 are highly conserved. The shape of α4/α6 pocket is alterable. The space of this pocket in ADP-binding state of Eg5 is larger than that in ADP·Pi-binding state due to the limitation of a hydrogen bond formed in the ADP·Pi-binding state. The results of this investigation provide the structural basis of the inhibitor-Eg5 interaction and offer a reference for the Eg5-targeted drug design.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 756
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 38641233
- Full Text :
- https://doi.org/10.1016/j.abb.2024.109998