5XLZ

The crystal structure of tubulin complexed with a benzylidene derivative of 9(10H)-anthracenone

Summary for 5XLZ

• Entry DOI: 10.2210/pdb5xlz/pdb
• Descriptor: Tubulin alpha-1B chain, 10-[(4-methoxy-3-oxidanyl-phenyl)methylidene]anthracen-9-one, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: inhibitor, tubulin, cell cycle
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• Total number of polymer chains: 6
• Total formula weight: 265047.50

Authors

Yu, Y.,Chen, Q. (deposition date: 2017-05-12, release date: 2017-11-22, Last modification date: 2024-03-27)

Primary citation

Cheng, J.,Wu, Y.,Wang, Y.,Wang, C.,Wang, Y.,Wu, C.,Zeng, S.,Yu, Y.,Chen, Q.
Structure of a benzylidene derivative of 9(10H)-anthracenone in complex with tubulin provides a rationale for drug design.
Biochem. Biophys. Res. Commun., 495:185-188, 2018

PubMed Abstract: Microtubules are composed of αβ-tubulin heterodimers and have been treated as highly attractive targets for antitumor drugs. A broad range of agents bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Tubulin Polymerization Inhibitor I (TPI1), a benzylidene derivative of 9(10H)-anthracenone, is a CBSI that inhibits the assembly of microtubules. However, for a long time, the design and development of anthracenone family drugs have been hindered by the lack of structural information of the tubulin-agent complex. Here we report a 2.3 Å crystal structure of tubulin complexed with TPI1, the first structure of anthracenone family agents. This complex structure reveals the interactions between TPI1 and tubulin, and thus provides insights into the development of new anthracenone derivatives targeting the colchicine binding site.

PubMed: 29102632
DOI: 10.1016/j.bbrc.2017.10.104

Experimental method

X-RAY DIFFRACTION (2.298 Å)