2WOG

Intermediate and final states of human kinesin Eg5 in complex with S-trityl-L-cysteine

2WOG の概要

• エントリーDOI: 10.2210/pdb2wog/pdb
• 関連するPDBエントリー: 1II6 1Q0B 1X88 1YRS 2FKY 2FL2 2FL6 2G1Q 2GM1 2UYI 2UYM
• 分子名称: KINESIN-LIKE PROTEIN KIF11, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: atp-binding, motor protein, mitosis, cell cycle, microtubule, cell division, phosphoprotein, nucleotide-binding
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 125611.68

構造登録者

Kaan, H.Y.K.,Ulaganathan, V.,Hackney, D.D.,Kozielski, F. (登録日: 2009-07-23, 公開日: 2010-08-04, 最終更新日: 2023-12-20)

主引用文献

Kaan, H.Y.K.,Ulaganathan, V.,Hackney, D.D.,Kozielski, F.
An Allosteric Transition Trapped in an Intermediate State of a New Kinesin-Inhibitor Complex.
Biochem.J., 425:55-, 2010

PubMed Abstract: Human kinesin Eg5 plays an essential role in mitosis by separating duplicated centrosomes and establishing the bipolar spindle. Eg5 is an interesting drug target for the development of cancer chemotherapy, with seven inhibitors already in clinical trials. In the present paper, we report the crystal structure of the Eg5 motor domain complexed with a potent antimitotic inhibitor STLC (S-trityl-L-cysteine) to 2.0 A (1 A=0.1 nm) resolution. The Eg5-STLC complex crystallizes in space group P3(2) with three molecules per asymmetric unit. Two of the molecules reveal the final inhibitor-bound state of Eg5, whereby loop L5 has swung downwards to close the inhibitor-binding pocket, helix alpha4 has rotated by approx. 15 degrees and the neck-linker has adopted a docked conformation. The third molecule, however, revealed an unprecedented intermediate state, whereby local changes at the inhibitor-binding pocket have not propagated to structural changes at the switch II cluster and neck-linker. This provides structural evidence for the sequence of drug-induced conformational changes.

PubMed: 19793049
DOI: 10.1042/BJ20091207

実験手法

X-RAY DIFFRACTION (2 Å)