7dae | pdb_00007dae

EPB in complex with tubulin

spinqualitylabelsall models 7dae, resolution 2.39Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7dae is a 6 chain structure with sequence from Gallus gallus, Mus musculus and Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.394Å Ligands: ACP, CA, CL, EPB, GDP, GTP, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TBB_PIG 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 Microtubule is a key component of cytoskeleton and has been considered as an important target for the treatment of cancer. In particular, the tubulin taxane-site inhibitors such as taxol analogs and epothilones have achieved great success in clinical trials. However, the structural basis of many taxane-site inhibitors is still lacking in exploring their mechanism of action. We here reported crystal complex structures for three taxane-site inhibitors, Ixabepilone, Epothilone B, and Epothilone D, which were determined to 2.4 A, 2.4 A, and 2.85 A, respectively. The crystal structures revealed that these taxane-site inhibitors possess similar binding modes to that of Epothilone A at the taxane site, e.g. making critical hydrogen-bonding interactions with multiple residues on the M-loop, which facilitating the tubulin polymerization. Furthermore, we summarized the binding modes of almost all taxane-site inhibitors and identified novel taxane-site ligands with simpler chemical structures through virtual screening. On this basis, new derivatives with higher binding affinity to tubulin were designed and developed, which can form additional hydrogen bond interactions with tubulin. Overall, this work determined the mechanism of action of epothilones and provided a structural basis to design reasonably novel taxane-site inhibitors with simpler structure and improved pharmacokinetic properties. High-resolution X-ray structure of three microtubule-stabilizing agents in complex with tubulin provide a rationale for drug design.,Xiao Q, Xue T, Shuai W, Wu C, Zhang Z, Zhang T, Zeng S, Sun B, Wang Y Biochem Biophys Res Commun. 2021 Jan 1;534:330-336. doi: , 10.1016/j.bbrc.2020.11.082. Epub 2020 Nov 30. PMID:33272565 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Stathmin-4 3D structures Tubulin 3D Structures Tubulin tyrosine ligase

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