PDBsum entry 6y6d

Cell cycle

PDB id: 6y6d

Contents

Protein chains

439 a.a.

422 a.a.

122 a.a.

333 a.a.

Ligands

GTP ×2

GDP ×2

OBQ ×2

MES

GOL

ACP

Metals

_CA ×2

_MG ×5

Waters ×506

PDB id:

6y6d

Name:

Cell cycle

Title:

Tubulin-7-aminonoscapine complex

Structure:

Tubulin alpha-1b chain. Chain: a, c. Synonym: alpha-tubulin ubiquitous,tubulin k-alpha-1,tubulin alpha- ubiquitous chain. Tubulin beta-2b chain. Chain: b, d. Stathmin-4. Chain: e. Synonym: stathmin-like protein b3,rb3.

Source:

Bos taurus. Cattle. Organism_taxid: 9913. Organ: brain. Bovine. Rattus norvegicus. Norway rat. Organism_taxid: 10116. Tissue: brain.

Resolution:

2.20Å R-factor: 0.186 R-free: 0.224

Authors:

M.A.Oliva,A.E.Prota,J.Rodriguez-Salarichs,W.Gu,Y.L.Bennani,J.Jimenez- Barbero,A.Canales,M.O.Steinmetz,J.F.Diaz

Key ref:

M.A.Oliva et al. (2020). Structural Basis of Noscapine Activation for Tubulin Binding. J Med Chem, 63, 8495-8501. PubMed id: 32657585 DOI: 10.1021/acs.jmedchem.0c00855

Date:

26-Feb-20 Release date: 22-Jul-20

Protein chains

P81947  (TBA1B_BOVIN) -  Tubulin alpha-1B chain from Bos taurus

Seq: 451 a.a.

Struc: 439 a.a.

Protein chains

Q6B856  (TBB2B_BOVIN) -  Tubulin beta-2B chain from Bos taurus

Seq: 445 a.a.

Struc: 422 a.a.

Protein chain

P63043  (STMN4_RAT) -  Stathmin-4 from Rattus norvegicus

Seq: 189 a.a.

Struc: 122 a.a.

Protein chain

E1BQ43  (E1BQ43_CHICK) -

DOI no: 10.1021/acs.jmedchem.0c00855

J Med Chem 63:8495-8501 (2020)

PubMed id: 32657585

Structural Basis of Noscapine Activation for Tubulin Binding.

M.A.Oliva, A.E.Prota, J.Rodríguez-Salarichs, Y.L.Bennani, J.Jiménez-Barbero, K.Bargsten, �.�.Canales, M.O.Steinmetz, J.F.Díaz.

ABSTRACT

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.