5t45

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

spinqualitylabelsall models 5t45, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5t45 is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 52E, ADP, BCN, BEF, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 (IC50 = 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. Highly selective inhibition of myosin motors provides the basis of potential therapeutic application.,Sirigu S, Hartman JJ, Planelles-Herrero VJ, Ropars V, Clancy S, Wang X, Chuang G, Qian X, Lu PP, Barrett E, Rudolph K, Royer C, Morgan BP, Stura EA, Malik FI, Houdusse AM Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7448-E7455. Epub 2016 Nov 4. PMID:27815532 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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