https://orcid.org/0000-0002-5784-2503
Abstract
Background: Tubulin protein is a promising target for antitumor drugs. Some tubulin inhibitors targeting the colchicine binding site are not substrates of the multidrug-resistance efflux pump, which can overcome the mechanism of drug resistance mediated by P-glycoprotein. Methodology/results: SSE15206 is a colchicine binding site inhibitor with antiproliferative activity against different drug-resistant cell lines. Unfortunately, the lack of detailed interaction information about SSE15206 in complex with tubulin impeded the development of potent drugs that possess similar scaffolds. Herein, the authors report the crystal structure of the tubulin–SSE15206 complex at a resolution of 2.8 Å. Conclusion: The complex structure reveals the intermolecular interactions between SSE15206 and tubulin, providing a rationale for the development of pyrazolinethioamides as tubulin polymerization inhibitors and to overcome multidrug resistance.
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Author contributions
Q Sun conceived and supervised the study; L Ma and J Lei designed and performed the experiments; L Ma, H Chen and R Huang collected the data, Q Sun, L Ma, T Su and J Feng analyzed the data; L Ma wrote the manuscript; Q Sun and J Feng revised the manuscript.
Acknowledgments
The authors would like to thank Y Wang for their comments on the manuscript and technical assistance. And the staff of BL17U1, BL18U and BL19U1 beamlines of the National Facility for Protein Science Shanghai (NFPS) at Shanghai Synchrotron Radiation Facility for assistance during data collection.
Financial & competing interests disclosure
This work was supported by the National Natural Science Foundation of China (31900866 to J Feng), the Doctors' Start-up and Initiation Grants of the Affiliated Hospital of Southwest Medical University (16227 to J Feng) and the research funding of the Southwest Medical University (00031020 to J Feng). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Data availability
The atomic coordinates and structure factors for the tubulin–SSE15206 complex have been deposited in the Protein Data Bank under accession code 7DBB.