9B00
Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with berberine analog of chloramphenicol CAM-BER, mRNA, deacylated A- and E-site tRNAphe, and deacylated P-site tRNAmet at 2.80A resolution
This is a non-PDB format compatible entry.
Summary for 9B00
| Entry DOI | 10.2210/pdb9b00/pdb |
| Descriptor | 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (61 entities in total) |
| Functional Keywords | chloramphenicol; berberine; antibiotic; 70s ribosome; x-ray structure; translation inhibitor; binding affinity; peptidyl transferase center; nascent peptide exit tunnel, ribosome |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 112 |
| Total formula weight | 4569739.59 |
| Authors | Batool, Z.,Pavlova, J.A.,Paranjpe, M.N.,Tereshchenkov, A.G.,Lukianov, D.A.,Osterman, I.A.,Bogdanov, A.A.,Sumbatyan, N.V.,Polikanov, Y.S. (deposition date: 2024-03-11, release date: 2024-08-07, Last modification date: 2025-03-19) |
| Primary citation | Batool, Z.,Pavlova, J.A.,Paranjpe, M.N.,Tereshchenkov, A.G.,Lukianov, D.A.,Osterman, I.A.,Bogdanov, A.A.,Sumbatyan, N.V.,Polikanov, Y.S. Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity. Structure, 32:1429-, 2024 Cited by PubMed Abstract: Chloramphenicol (CHL) is an antibiotic targeting the peptidyl transferase center in bacterial ribosomes. We synthesized a new analog, CAM-BER, by substituting the dichloroacetyl moiety of CHL with a positively charged aromatic berberine group. CAM-BER suppresses bacterial cell growth, inhibits protein synthesis in vitro, and binds tightly to the 70S ribosome. Crystal structure analysis reveals that the bulky berberine group folds into the P site of the peptidyl transferase center (PTC), where it competes with the formyl-methionine residue of the initiator tRNA. Our toe-printing data confirm that CAM-BER acts as a translation initiation inhibitor in stark contrast to CHL, a translation elongation inhibitor. Moreover, CAM-BER induces a distinct rearrangement of conformationally restrained nucleotide A2059, suggesting that the 23S rRNA plasticity is significantly higher than previously thought. CAM-BER shows potential in avoiding CHL resistance and presents opportunities for developing novel berberine derivatives of CHL through medicinal chemistry exploration. PubMed: 39019034DOI: 10.1016/j.str.2024.06.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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