9HL9
CRYO-EM STRUCTURE OF LEISHMANIA MAJOR 80S RIBOSOME WITH P/E-site tRNA AND mRNA : LM14Cs1H3 sKO STRAIN
This is a non-PDB format compatible entry.
Summary for 9HL9
| Entry DOI | 10.2210/pdb9hl9/pdb |
| EMDB information | 52247 |
| Descriptor | LSUa_rRNA, Putative ribosomal protein L3, Putative ribosomal protein L1a, ... (94 entities in total) |
| Functional Keywords | cryo-em, leishmania major, 80s, ribosome, lm14cs1h3, snorna |
| Biological source | Leishmania major strain Friedlin More |
| Total number of polymer chains | 88 |
| Total formula weight | 3600556.77 |
| Authors | Rajan, K.S.,Yonath, A. (deposition date: 2024-12-04, release date: 2025-10-15, Last modification date: 2025-11-19) |
| Primary citation | Bora Bhowal, K.,Nguyen, A.M.T.,Ibarra-Meneses, A.V.,Brito Lira, A.,Rajan, K.S.,Castano, J.D.,Beaudry, F.,Bashan, A.,Fernandez-Prada, C.,Olivier, M.,Yonath, A.,Lubell, W.D. p -Alkoxy-Substituted Anisomycins with Potent Anti-Trypanosomiasis Activity and Expanded Modes of Action. J.Med.Chem., 68:20264-20282, 2025 Cited by PubMed Abstract: Neglected tropical diseases caused by trypanosomatid parasites present a major public healthcare issue, partly due to emerging resistance. Attachment of ω-alkynyl chains characteristic of the lipid tails of antiparasitic peptides to the -position of anisomycin gave ethers exhibiting potent activity, rivalling that of the parent ribosomal inhibitor, especially against resistant strains. Single-particle cryoelectron microscopy analysis revealed that -propargyl anisomycin binds to the highly conserved peptidyl transferase center of the ribosome similar to the parent inhibitor. Thermal proteomic profiling and gene ontology analysis demonstrated that -propargyl anisomycin exhibited a broader mode of action, including activity against glycosome-associated proteins. Alkynyl substituents improved antiparasitic activity against resistant strains, likely by enlarging the mode of action, offering a novel path toward therapy against trypanosomatid infections. PubMed: 40980996DOI: 10.1021/acs.jmedchem.5c01291 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.5 Å) |
Structure validation
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