%0 Journal Article
%A Canales Mayordomo, María Ángeles
%A Bargsten, Katja
%A Bennani, Youssef L.
%A Díaz, Fernando J.
%A Jiménez Barbero, Jesús
%A Oliva, María A.
%A Prota, Andrea E.
%A Rodríguez Salarichs, J.
%A Steinmetz, Michel O.
%T Structural basis of noscapine activation for tubulin binding
%D 2020
%U https://hdl.handle.net/20.500.14352/129977
%X Noscapine is a natural alkaloid that is used as an antitussive medicine. However, it also acts as a weak anticancer agent in certain in vivo models through a mechanism that is largely unknown. Here, we performed structural studies and show that the cytotoxic agent 7A-O-demethoxy-amino-noscapine (7A-aminonoscapine) binds to the colchicine site of tubulin. We suggest that the 7A-methoxy group of noscapine prevents binding to tubulin due to a steric clash of the compound with the T5-loop of α-tubulin. We further propose that the anticancer activity of noscapine arises from a bioactive metabolite that binds to the colchicine site of tubulin to induce mitotic arrest through a microtubule cytoskeleton-based mechanism.
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