5T45

Chicken smooth muscle myosin motor domain co-crystallized with the specific CK-571 inhibitor, MgADP.BeFx form

5T45 の概要

• エントリーDOI: 10.2210/pdb5t45/pdb
• 分子名称: Myosin-11, 4-{[(2-chloro-3-fluorobenzyl)carbamoyl](methyl)amino}-3,4-dideoxy-5-O-(isoquinolin-3-ylcarbamoyl)-D-erythro-pentitol, MAGNESIUM ION, ... (8 entities in total)
• 機能のキーワード: myosin inhibitor, motor protein
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 93033.57

構造登録者

Sirigu, S.,Planelles-Herrero, V.J.,Hartman, J.,Houdusse, A. (登録日: 2016-08-29, 公開日: 2016-11-16, 最終更新日: 2024-01-17)

主引用文献

Sirigu, S.,Hartman, J.J.,Planelles-Herrero, V.J.,Ropars, V.,Clancy, S.,Wang, X.,Chuang, G.,Qian, X.,Lu, P.P.,Barrett, E.,Rudolph, K.,Royer, C.,Morgan, B.P.,Stura, E.A.,Malik, F.I.,Houdusse, A.M.
Highly selective inhibition of myosin motors provides the basis of potential therapeutic application.
Proc. Natl. Acad. Sci. U.S.A., 113:E7448-E7455, 2016

PubMed Abstract: Direct inhibition of smooth muscle myosin (SMM) is a potential means to treat hypercontractile smooth muscle diseases. The selective inhibitor CK-2018571 prevents strong binding to actin and promotes muscle relaxation in vitro and in vivo. The crystal structure of the SMM/drug complex reveals that CK-2018571 binds to a novel allosteric pocket that opens up during the "recovery stroke" transition necessary to reprime the motor. Trapped in an intermediate of this fast transition, SMM is inhibited with high selectivity compared with skeletal muscle myosin (IC = 9 nM and 11,300 nM, respectively), although all of the binding site residues are identical in these motors. This structure provides a starting point from which to design highly specific myosin modulators to treat several human diseases. It further illustrates the potential of targeting transition intermediates of molecular machines to develop exquisitely selective pharmacological agents.

PubMed: 27815532
DOI: 10.1073/pnas.1609342113

実験手法

X-RAY DIFFRACTION (2.8 Å)