5ZO7

Kinesin spindle protein Eg5 in complex with STLC-type inhibitor PVEI0138

5ZO7 の概要

• エントリーDOI: 10.2210/pdb5zo7/pdb
• 分子名称: Kinesin-like protein KIF11, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: motor domain, atp binding, cell cycle
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 84536.03

構造登録者

Yokoyama, H.,Sato, K. (登録日: 2018-04-12, 公開日: 2018-10-10, 最終更新日: 2024-03-27)

主引用文献

Yokoyama, H.,Sawada, J.I.,Sato, K.,Ogo, N.,Kamei, N.,Ishikawa, Y.,Hara, K.,Asai, A.,Hashimoto, H.
Structural and Thermodynamic Basis of the Enhanced Interaction between Kinesin Spindle Protein Eg5 and STLC-type Inhibitors.
Acs Omega, 3:12284-12294, 2018

PubMed Abstract: For a better understanding of protein-inhibitor interactions, we report structural, thermodynamic, and biological analyses of the interactions between -trityl-l-cysteine (STLC) derivatives and the motor domain of kinesin spindle protein Eg5. Binding of STLC-type inhibitors to Eg5 was enthalpically driven and entropically unfavorable. The introduction of a -methoxy substituent in one phenyl ring of STLC enhances its inhibitory activity resulting from a larger enthalpy gain possibly due to the increased shape complementarity. The substituent fits to a recess in the binding pocket. To avoid steric hindrance, the substituted STLC is nudged toward the side opposite to the recess, which enhances the interaction of Eg5 with the remaining part of the inhibitor. Further introduction of an ethylene linkage between two phenyl rings enhances Eg5 inhibitory activity by reducing the loss of entropy in forming the complex. This study provides valuable examples of enhancing protein-inhibitor interactions without forming additional hydrogen bonds.

PubMed: 31459302
DOI: 10.1021/acsomega.8b00778

実験手法

X-RAY DIFFRACTION (2.6 Å)