5XLT

The crystal structure of tubulin in complex with 4'-demethylepipodophyllotoxin

Summary for 5XLT

• Entry DOI: 10.2210/pdb5xlt/pdb
• Descriptor: Tubulin alpha-1B chain, (5S,5aR,8aR,9R)-9-(3,5-dimethoxy-4-oxidanyl-phenyl)-5-oxidanyl-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: tubulin, inhibitor, 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: 265111.56

Authors

Yu, Y.,Chen, Q. (deposition date: 2017-05-11, release date: 2017-09-27, Last modification date: 2024-03-27)

Primary citation

Niu, L.,Wang, Y.,Wang, C.,Wang, Y.,Jiang, X.,Ma, L.,Wu, C.,Yu, Y.,Chen, Q.
Structure of 4'-demethylepipodophyllotoxin in complex with tubulin provides a rationale for drug design
Biochem. Biophys. Res. Commun., 493:718-722, 2017

PubMed Abstract: Microtubules consists of αβ-tubulin heterodimers and are highly attractive targets for anti-cancer drugs. A broad range of agents have been identified to bind to tubulin and interfere with microtubule assembly, including colchicine binding site inhibitors (CBSIs). Podophyllotoxin is a CBSI that inhibits the assembly of microtubules. However, for a long time, the design and development of podophyllotoxin family drugs have been hindered by the lack of high-resolution structural information of the tubulin-agent complex. We report the first high-resolution (2.8 Å) structure of a podophyllotoxin family agent (4'-demethylepipodophyllotoxin, DMEP) complexed with tubulin and revealed the detailed interactions between DMEP and tubulin. Comparison of this structure and other CBSIs explains previous results of the structure-activity-relationship (SAR) studies, and provides insights into the development of new podophyllotoxin derivatives targeting the colchicine site.

PubMed: 28864414
DOI: 10.1016/j.bbrc.2017.08.125

Experimental method

X-RAY DIFFRACTION (2.813 Å)