1z2b

Tubulin-colchicine-vinblastine: stathmin-like domain complex

spinqualitylabelsall models 1z2b, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1z2b is a 5 chain structure with sequence from Bos taurus and Rattus norvegicus. The July 2014 RCSB PDB Molecule of the Month feature on Microtubules by David Goodsell is 10.2210/rcsb_pdb/mom_2014_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 4.1Å Ligands: CN2, GDP, GTP, MG, VLB Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TBA1D_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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Vinblastine is one of several tubulin-targeting Vinca alkaloids that have been responsible for many chemotherapeutic successes since their introduction in the clinic as antitumour drugs. In contrast with the two other classes of small tubulin-binding molecules (Taxol and colchicine), the binding site of vinblastine is largely unknown and the molecular mechanism of this drug has remained elusive. Here we report the X-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at the interface of two tubulin molecules and thus interferes with tubulin assembly. Together with electron microscopical and biochemical data, the structure explains vinblastine-induced tubulin self-association into spiral aggregates at the expense of microtubule growth. It also shows that vinblastine and the amino-terminal part of RB3-SLD binding sites share a hydrophobic groove on the alpha-tubulin surface that is located at an intermolecular contact in microtubules. This is an attractive target for drugs designed to perturb microtubule dynamics by interfacial interference, for which tubulin seems ideally suited because of its propensity to self-associate. Structural basis for the regulation of tubulin by vinblastine.,Gigant B, Wang C, Ravelli RB, Roussi F, Steinmetz MO, Curmi PA, Sobel A, Knossow M Nature. 2005 May 26;435(7041):519-22. PMID:15917812 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures

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