4yj2

Crystal structure of tubulin bound to MI-181

spinqualitylabelsall models 4yj2, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4yj2 is a 6 chain structure with sequence from [1] and Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 4ED, CA, GDP, GOL, GTP, IMD, MES, MG Related: 4yj3 Resources: FirstGlance, OCA, RCSB, PDBsum Function [TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [STMN4_RAT] Exhibits microtubule-destabilizing activity. [TBB2B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity). Publication Abstract from PubMed Small molecules that bind to tubulin exert powerful effects on cell division and apoptosis (programmed cell death). Cell-based high-throughput screening combined with chemo/bioinformatic and biochemical analyses recently revealed a novel compound MI-181 as a potent mitotic inhibitor with heightened activity towards melanomas. MI-181 causes tubulin depolymerization, activates the spindle assembly checkpoint arresting cells in mitosis, and induces apoptotic cell death. C2 is an unrelated compound previously shown to have lethal effects on microtubules in tumorigenic cell lines. We report 2.60 A and 3.75 A structures of MI-181 and C2, respectively, bound to a ternary complex of alphabeta-tubulin, the tubulin-binding protein stathmin, and tubulin tyrosine ligase. In the first of these structures, our crystallographic results reveal a unique binding mode for MI-181 extending unusually deep into the well-studied colchicine-binding site on beta-tubulin. In the second structure the C2 compound occupies the colchicine-binding site on beta-tubulin with two chemical moieties recapitulating contacts made by colchicine, in combination with another system of atomic contacts. These insights reveal the source of the observed effects of MI-181 and C2 on microtubules, mitosis, and cultured cancer cell lines. The structural details of the interaction between tubulin and the described compounds may guide the development of improved derivative compounds as therapeutic candidates or molecular probes to study cancer cell division. This article is protected by copyright. All rights reserved. Structures of potent anticancer compounds bound to tubulin.,McNamara DE, Senese S, Yeates TO, Torres JZ Protein Sci. 2015 May 13. doi: 10.1002/pro.2704. PMID:25970265 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tubulin

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