2XO8

Crystal Structure of Myosin-2 in Complex with Tribromodichloropseudilin

2XO8 の概要

• エントリーDOI: 10.2210/pdb2xo8/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 2XEL
• 分子名称: MYOSIN-2 HEAVY CHAIN, 2,4-DICHLORO-6-(3,4,5-TRIBROMO-1H-PYRROL-2-YL)PHENOL, ADP METAVANADATE, ... (5 entities in total)
• 機能のキーワード: motor protein
• 由来する生物種: DICTYOSTELIUM DISCOIDEUM
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 89471.11

構造登録者

Preller, M.,Chinthalapudi, K.,Martin, R.,Knoelker, H.J.,Manstein, D.J. (登録日: 2010-08-10, 公開日: 2011-05-25, 最終更新日: 2023-12-20)

主引用文献

Preller, M.,Chinthalapudi, K.,Martin, R.,Knolker, H.,Manstein, D.J.
Inhibition of Myosin ATPase Activity by Halogenated Pseudilins: A Structure-Activity Study.
J.Med.Chem., 54:3675-, 2011

PubMed Abstract: Myosin activity is crucial for many biological functions. Strong links have been established between changes in the activity of specific myosin isoforms and diseases such as cancer, cardiovascular failure, and disorders of sensory organs and the central nervous system. The modulation of specific myosin isoforms therefore holds a strong therapeutic potential. In recent work, we identified members of the marine alkaloid family of pseudilins as potent inhibitors of myosin-dependent processes. Here, we report the crystal structure of the complex between the Dictyostelium myosin 2 motor domain and 2,4-dichloro-6-(3,4,5-tribromo-1H-pyrrole-2-yl)phenol (3). Detailed comparison with previously solved structures of the myosin 2 complex with bound pentabromopseudilin (2a) or pentachloropseudilin (4a) provides insights into the molecular basis of the allosteric communication between the catalytic and the allosteric sites. Moreover, we describe the inhibitory potency for a congeneric series of halogenated pseudilins. Insight into their mode of action is gained by applying a combination of experimental and computational approaches.

PubMed: 21534527
DOI: 10.1021/JM200259F

実験手法

X-RAY DIFFRACTION (2.4 Å)