2xel

Molecular Mechanism of Pentachloropseudilin Mediated Inhibition of Myosin Motor Activity

spinqualitylabelsall models 2xel, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xel is a 1 chain structure with sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Ligands: AD9, IA2, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MYS2_DICDI Myosin is a protein that binds to actin and has ATPase activity that is activated by actin. Publication Abstract from PubMed 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 mum for mammalian class-1 myosins and greater than 90 mum 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. Mechanism and Specificity of Pentachloropseudilin-mediated Inhibition of Myosin Motor Activity.,Chinthalapudi K, Taft MH, Martin R, Heissler SM, Preller M, Hartmann FK, Brandstaetter H, Kendrick-Jones J, Tsiavaliaris G, Gutzeit HO, Fedorov R, Buss F, Knolker HJ, Coluccio LM, Manstein DJ J Biol Chem. 2011 Aug 26;286(34):29700-8. Epub 2011 Jun 16. PMID:21680745 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Myosin 3D Structures

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