7en3

Crystal structure of tubulin in complex with Tubulysin analogue TGL

spinqualitylabelsall models 7en3, resolution 2.64Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7en3 is a 6 chain structure with sequence from Bos taurus, Gallus gallus, Rattus norvegicus 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 2.643Å Ligands: ACP, CA, GDP, GTP, J6R, MES, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TBA1B_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-targeting agents (MTAs) are the most commonly used anti-cancer drugs. At least fourteen microtubule inhibitors and ten antibody drug conjugates (ADCs) linking MTAs are approved by FDA for clinical use in cancer therapy. In current research, we determined the crystal structure of tubulysin analogue TGL in complex with tubulin at a high resolution (2.65 A). In addition, we summarized all of the previously published high-resolution crystal structures of ligands in the vinca site to provide structural insights for the rational design of the new vinca-site ligands. Moreover, based on the aligned results of the vinca site ligands, we provided three possible routes for designing new tubulysin analogues, namely macrocyclization between the N-14 side chain and the N-9 side chain, the hybird of tubulysin M and phomopsin A, and growing new aryl group at C-21. These designed structures will inspire the development of new MTAs or payloads in cancer therapy. The X-ray structure of tubulysin analogue TGL in complex with tubulin and three possible routes for the development of next-generation tubulysin analogues.,Li W, Tan L, Zhang Z, Xia Q, Lei D, Li Y, Zhang T, Zeng S, Sima X, Wang Y Biochem Biophys Res Commun. 2021 Aug 6;565:29-35. doi: , 10.1016/j.bbrc.2021.05.086. Epub 2021 Jun 2. PMID:34090207 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tubulin 3D Structures Tubulin tyrosine ligase

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