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

spinqualitylabelsall models 9b00, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9b00 is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: 0TD, 2MA, 2MG, 4OC, 4SU, 5MC, 5MU, A1AIX, G7M, K, M2G, MA6, MG, MIA, OMC, OMG, OMU, PSU, SF4, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL3_THET8 One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit (By similarity).[HAMAP-Rule:MF_01325_B] Publication Abstract from PubMed 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. Berberine analog of chloramphenicol exhibits a distinct mode of action and unveils ribosome plasticity.,Batool Z, Pavlova JA, Paranjpe MN, Tereshchenkov AG, Lukianov DA, Osterman IA, Bogdanov AA, Sumbatyan NV, Polikanov YS Structure. 2024 Jul 6:S0969-2126(24)00231-4. doi: 10.1016/j.str.2024.06.013. PMID:39019034 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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