12dp

Crystal structure of the wild-type Thermus thermophilus 70S ribosome in complex with sparsomycin, mRNA, and aminoacylated initiator P-site fMet-tRNAmet at 2.95A resolution

spinqualitylabelsall models 12dp, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 12dp 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 2.95Å Ligands: 0TD, 2MA, 2MG, 4OC, 4SU, 5MC, 5MU, 8AN, FME, G7M, K, M2G, MA6, MG, OMC, OMG, OMU, PSU, SPS, UR3, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL2_THET8 One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_B] Publication Abstract from PubMed Sparsomycin (SPA) is a broad-spectrum inhibitor of protein synthesis with activity across all three domains of life. Although SPA has long been known to target the ribosomal peptidyl transferase center (PTC), previous structural studies suggested that SPA binds differently to bacterial ribosomes compared to their archaeal and eukaryotic counterparts-an unexpected conclusion given the high evolutionary conservation of the ribosomal catalytic center. Here, we show that SPA inhibits a majority of elongation-competent bacterial ribosomal complexes and present X-ray crystal structures of Thermus thermophilus 70S ribosomes stalled by SPA at the initiation and early elongation stages of translation. These structures reveal that SPA binds to the bacterial ribosome in a manner essentially identical to that observed in archaeal and eukaryotic ribosomes, establishing a unified structural mechanism of SPA action across all domains of life. In this conserved binding mode, SPA occupies the A-site cleft of the PTC and forms an extensive network of interactions with universally conserved ribosomal RNA nucleotides and the CCA-end of the P-site transfer RNA (tRNA), thereby stabilizing the peptidyl-tRNA substrate while sterically blocking accommodation of an incoming aminoacyl-tRNA. By clarifying the mode of action of SPA on the bacterial ribosome, our work provides a structural framework for the rational design of SPA derivatives with improved potency and bacterial specificity. Sparsomycin inhibits translation through a conserved mechanism across all domains of life.,Paranjpe MN, Leroy EC, Syroegin EA, Flemmich L, Thaler J, Gillard M, Bougas A, Kournoutou G, Dinos GP, Renault TT, Micura R, Innis CA, Polikanov YS Nucleic Acids Res. 2026 Aug 10;54(15):gkag761. doi: 10.1093/nar/gkag761. PMID:42581761 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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