6Y6X

Tetracenomycin X bound to the human ribosome

This is a non-PDB format compatible entry.

Summary for 6Y6X

• Entry DOI: 10.2210/pdb6y6x/pdb
• EMDB information: 10709
• Descriptor: 28S ribosomal RNA, 60S ribosomal protein L7a, 60S ribosomal protein L9, ... (49 entities in total)
• Functional Keywords: translation inhibitor, antibiotic
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 46
• Total formula weight: 2522979.29

Authors

Buschauer, R.,Cheng, J.,Berninghausen, O.,Beckmann, R.,Wilson, D.N. (deposition date: 2020-02-27, release date: 2020-07-08, Last modification date: 2023-11-08)

Primary citation

Osterman, I.A.,Wieland, M.,Maviza, T.P.,Lashkevich, K.A.,Lukianov, D.A.,Komarova, E.S.,Zakalyukina, Y.V.,Buschauer, R.,Shiriaev, D.I.,Leyn, S.A.,Zlamal, J.E.,Biryukov, M.V.,Skvortsov, D.A.,Tashlitsky, V.N.,Polshakov, V.I.,Cheng, J.,Polikanov, Y.S.,Bogdanov, A.A.,Osterman, A.L.,Dmitriev, S.E.,Beckmann, R.,Dontsova, O.A.,Wilson, D.N.,Sergiev, P.V.
Tetracenomycin X inhibits translation by binding within the ribosomal exit tunnel.
Nat.Chem.Biol., 16:1071-1077, 2020

PubMed Abstract: The increase in multi-drug resistant pathogenic bacteria is making our current arsenal of clinically used antibiotics obsolete, highlighting the urgent need for new lead compounds with distinct target binding sites to avoid cross-resistance. Here we report that the aromatic polyketide antibiotic tetracenomycin (TcmX) is a potent inhibitor of protein synthesis, and does not induce DNA damage as previously thought. Despite the structural similarity to the well-known translation inhibitor tetracycline, we show that TcmX does not interact with the small ribosomal subunit, but rather binds to the large subunit, within the polypeptide exit tunnel. This previously unappreciated binding site is located adjacent to the macrolide-binding site, where TcmX stacks on the noncanonical basepair formed by U1782 and U2586 of the 23S ribosomal RNA. Although the binding site is distinct from the macrolide antibiotics, our results indicate that like macrolides, TcmX allows translation of short oligopeptides before further translation is blocked.

PubMed: 32601485
DOI: 10.1038/s41589-020-0578-x

Experimental method

ELECTRON MICROSCOPY (2.8 Å)