2XEL

Molecular Mechanism of Pentachloropseudilin Mediated Inhibition of Myosin Motor Activity

2XEL の概要

• エントリーDOI: 10.2210/pdb2xel/pdb
• 関連するPDBエントリー: 1D0X 1D0Y 1D0Z 1D1A 1D1B 1D1C 1FMV 1FMW 1G8X 1JWY 1JX2 1LVK 1MMA 1MMD 1MMG 1MMN 1MND 1MNE 1Q5G 1VOM 1W9I 1W9J 1W9K 1W9L 1YV3 2AKA 2JHR 2JJ9 2X9H
• 分子名称: MYOSIN-2 HEAVY CHAIN, ADP METAVANADATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: contractile protein, allosteric inhibitor, non-hydroylsable atp analogue, motor protein
• 由来する生物種: DICTYOSTELIUM DISCOIDEUM (SLIME MOLD)
• 細胞内の位置: Cytoplasm, cell cortex: P08799
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 89396.83

構造登録者

Chinthalapudi, K.,Taft, M.H.,Martin, R.,Hartmann, F.K.,Heissler, S.M.,Tsiavaliaris, G.,Gutzeit, H.O.,Knoelker, H.J.,Coluccio, L.M.,Fedorov, R.,Manstein, D.J. (登録日: 2010-05-16, 公開日: 2011-06-15, 最終更新日: 2024-05-08)

主引用文献

Chinthalapudi, K.,Taft, M.H.,Martin, R.,Heissler, S.M.,Preller, M.,Hartmann, F.K.,Brandstaetter, H.,Kendrick-Jones, J.,Tsiavaliaris, G.,Gutzeit, H.O.,Fedorov, R.,Buss, F.,Knoelker, H.J.,Coluccio, L.M.,Manstein, D.J.
Mechanism and Specificity of Pentachloropseudilin-Mediated Inhibition of Myosin Motor Activity.
J.Biol.Chem., 286:29700-, 2011

PubMed Abstract: Here, we report that the natural compound pentachloropseudilin (PClP) acts as a reversible and allosteric inhibitor of myosin ATPase and motor activity. IC(50) values are in the range from 1 to 5 μm for mammalian class-1 myosins and greater than 90 μm for class-2 and class-5 myosins, and no inhibition was observed with class-6 and class-7 myosins. We show that in mammalian cells, PClP selectively inhibits myosin-1c function. To elucidate the structural basis for PClP-induced allosteric coupling and isoform-specific differences in the inhibitory potency of the compound, we used a multifaceted approach combining direct functional, crystallographic, and in silico modeling studies. Our results indicate that allosteric inhibition by PClP is mediated by the combined effects of global changes in protein dynamics and direct communication between the catalytic and allosteric sites via a cascade of small conformational changes along a conserved communication pathway.

PubMed: 21680745
DOI: 10.1074/JBC.M111.239210

実験手法

X-RAY DIFFRACTION (2.5 Å)