5mf4

Tubulin-Dictyostatin complex

spinqualitylabelsall models 5mf4, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5mf4 is a 6 chain structure with sequence from Bos taurus, Gallus gallus and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: 7LZ, ACP, CA, GDP, GOL, GTP, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin-dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure-activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents. Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells.,Trigili C, Barasoain I, Sanchez-Murcia PA, Bargsten K, Redondo-Horcajo M, Nogales A, Gardner NM, Meyer A, Naylor GJ, Gomez-Rubio E, Gago F, Steinmetz MO, Paterson I, Prota AE, Diaz JF ACS Omega. 2016 Dec 31;1(6):1192-1204. doi: 10.1021/acsomega.6b00317. Epub 2016, Dec 13. PMID:30023505 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures

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