6JCJ

Structure of crolibulin in complex with tubulin

Summary for 6JCJ

• Entry DOI: 10.2210/pdb6jcj/pdb
• Descriptor: Tubulin alpha-1B chain, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, Tubulin beta-2B chain, ... (11 entities in total)
• Functional Keywords: cbsis, colchicine binding site inhibitors, cell cycle
• Biological source: Sus scrofa (Pig); More
• Total number of polymer chains: 6
• Total formula weight: 264810.51

Authors

Zhang, Z.,Yang, J. (deposition date: 2019-01-29, release date: 2019-03-13, Last modification date: 2023-11-22)

Primary citation

Zhang, Z.,Wang, C.,Ma, L.,Jiang, X.,Wu, C.,Wang, Y.,Jiang, Y.,Zheng, W.,Yang, Y.,Ma, Y.,Yang, J.
Molecular mechanism of crolibulin in complex with tubulin provides a rationale for drug design.
Biochem. Biophys. Res. Commun., 511:381-386, 2019

PubMed Abstract: Microtubules (MTs) is one of the most important proteins in eukaryotic cells and plays a key role in the maintenance of cell morphology and cell division. The discovery and development of small molecule drugs targeting MTs has always been an important direction of anti-cancer research. Nowadays 4-Aryl-4H-chromenes have emerged as potent microtubule-targeting agents (MTAs) for various cancers. Crolibulin, a derivative of 4-Aryl-4H-chromenes, which has been progressed to Phase I/II clinical testing's for anaplastic thyroid cancer with the National Cancer Institute. However, the design and development of 4-Aryl-4H-chromenes family drugs have been hindered for a long time by the lack of structural information of the tubulin-agent complex. Here we report a 2.5 Å crystal structure of tubulin complexed with crolibulin. This complex structure reveals the interactions between crolibulin and tubulin, helps explain the results of the structure-activity-relationship (SAR) studies and provides a solid structural basis for the design and development of new 4-Aryl-4H-chromenes derivatives as MTAs.

PubMed: 30803758
DOI: 10.1016/j.bbrc.2019.02.064

Experimental method

X-RAY DIFFRACTION (2.5 Å)