5SBE

Tubulin-maytansinoid-5c-complex

Summary for 5SBE

• Entry DOI: 10.2210/pdb5sbe/pdb
• Group deposition: T2R-TTL-maytansinoid structures (G_1002215)
• Descriptor: Tubulin alpha-1B chain, (1S,2R,3S,5S,6S,16E,18E,20R)-11-chloro-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.1~10,14~.0~3,5~]hexacosa-10(26),11,13,16,18,21-hexaen-6-yl hept-6-ynoate, PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: cell cycle, tubulin fold, cytoskeleton, microtubule
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 6
• Total formula weight: 265161.47

Authors

Marzullo, P.,Boiarska, Z.,Perez-Pena, H.,Abel, A.-C.,Alvarez-Bernad, B.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Steinmetz, M.O.,Prota, A.E.,Diaz, J.F.,Pieraccini, S.,Passarella, D. (deposition date: 2021-07-20, release date: 2021-12-08, Last modification date: 2024-05-22)

Primary citation

Marzullo, P.,Boiarska, Z.,Perez-Pena, H.,Abel, A.C.,Alvarez-Bernad, B.,Lucena-Agell, D.,Vasile, F.,Sironi, M.,Altmann, K.H.,Prota, A.E.,Diaz, J.F.,Pieraccini, S.,Passarella, D.
Maytansinol Derivatives: Side Reactions as a Chance for New Tubulin Binders.
Chemistry, 28:e202103520-e202103520, 2022

PubMed Abstract: Maytansinol is a valuable precursor for the preparation of maytansine derivatives (known as maytansinoids). Inspired by the intriguing structure of the macrocycle and the success in targeted cancer therapy of the derivatives, we explored the maytansinol acylation reaction. As a result, we were able to obtain a series of derivatives with novel modifications of the maytansine scaffold. We characterized these molecules by docking studies, by a comprehensive biochemical evaluation, and by determination of their crystal structures in complex with tubulin. The results shed further light on the intriguing chemical behavior of maytansinoids and confirm the relevance of this peculiar scaffold in the scenario of tubulin binders.

PubMed: 34788896
DOI: 10.1002/chem.202103520

Experimental method

X-RAY DIFFRACTION (2.75 Å)