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PDBsum entry 6y6d
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Contents |
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439 a.a.
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422 a.a.
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122 a.a.
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333 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis of noscapine activation for tubulin binding.
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Authors
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M.A.Oliva,
A.E.Prota,
J.Rodríguez-Salarichs,
Y.L.Bennani,
J.Jiménez-Barbero,
K.Bargsten,
..Canales,
M.O.Steinmetz,
J.F.Díaz.
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Ref.
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J Med Chem, 2020,
63,
8495-8501.
[DOI no: ]
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PubMed id
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Abstract
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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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