4I50

Crystal structure of tubulin-stathmin-TTL-Epothilone A complex

Summary for 4I50

• Entry DOI: 10.2210/pdb4i50/pdb
• Related: 4I4T 4I55 4IHJ 4IIJ
• Descriptor: Tubulin alpha-1B chain, GUANOSINE-5'-DIPHOSPHATE, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (14 entities in total)
• Functional Keywords: alpha-tubulin, beta-tubulin, ligase, gtpase, microtubule, stathmin, epothilone a, cell cycle
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cytoplasm, cytoskeleton: P81947 Q6B856; Golgi apparatus : P63043
• Total number of polymer chains: 6
• Total formula weight: 265651.46

Authors

Prota, A.E.,Bargsten, K.,Zurwerra, D.,Field, J.J.,Diaz, J.F.,Altmann, K.H.,Steinmetz, M.O. (deposition date: 2012-11-28, release date: 2013-01-23, Last modification date: 2023-09-20)

Primary citation

Prota, A.E.,Bargsten, K.,Zurwerra, D.,Field, J.J.,Diaz, J.F.,Altmann, K.H.,Steinmetz, M.O.
Molecular Mechanism of Action of Microtubule-Stabilizing Anticancer Agents.
Science, 339:587-590, 2013

PubMed Abstract: Microtubule-stabilizing agents (MSAs) are efficacious chemotherapeutic drugs widely used for the treatment of cancer. Despite the importance of MSAs for medical applications and basic research, their molecular mechanisms of action on tubulin and microtubules remain elusive. We determined high-resolution crystal structures of αβ-tubulin in complex with two unrelated MSAs, zampanolide and epothilone A. Both compounds were bound to the taxane pocket of β-tubulin and used their respective side chains to induce structuring of the M-loop into a short helix. Because the M-loop establishes lateral tubulin contacts in microtubules, these findings explain how taxane-site MSAs promote microtubule assembly and stability. Further, our results offer fundamental structural insights into the control mechanisms of microtubule dynamics.

PubMed: 23287720
DOI: 10.1126/science.1230582

Experimental method

X-RAY DIFFRACTION (2.3 Å)