6KPP
BNC105 in complex with tubulin
Summary for 6KPP
| Entry DOI | 10.2210/pdb6kpp/pdb |
| Descriptor | Tubulin alpha-1B chain, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, GLYCEROL, ... (12 entities in total) |
| Functional Keywords | bnc105, tubulin, protein-drug complex, antitumor protein |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 6 |
| Total formula weight | 264734.52 |
| Authors | |
| Primary citation | Wang, T.,Wu, C.,Wang, C.,Zhang, G.,Arnst, K.E.,Yao, Y.,Zhang, Z.,Wang, Y.,Pu, D.,Li, W. Unraveling the molecular mechanism of BNC105, a phase II clinical trial vascular disrupting agent, provides insights into drug design. Biochem.Biophys.Res.Commun., 2020 Cited by PubMed Abstract: Microtubules are made up of tubulin protein and play a very important part in numerous cellular events of eukaryotic cells, which is why they are seen as attractive targets for tumor chemotherapy. BNC105, a known vascular targeting agent, has entered in phase II clinical trials. It has previously been confirmed that BNC105 is an effective microtubule targeting agent for various cancers. BNC105 exhibits selectivity for tumor cells, elicits vascular disrupting effects, and inhibits tumor growth. However, the molecular mechanism of BNC105 is still elusive. Herein, the crystal structure of BNC105 in complex with tubulin protein is revealed, demonstrating the its interaction with the colchicine binding site. In order to thoroughly evaluate its molecular mechanism from a structural-activity-relationship standpoint, the binding mode of tubulin to BNC-105 is compared with colchicine, CA-4 and other BNC-105 derivatives. Our study not only confirms the detailed interactions of the BNC105-tubulin complex, but also offer substantial structural foundation for the design and development of novel benzo[b]furan derivatives as microtubule targeting agents. PubMed: 32085900DOI: 10.1016/j.bbrc.2019.12.083 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.74524106157 Å) |
Structure validation
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