Summary for 7MDZ
| Entry DOI | 10.2210/pdb7mdz/pdb |
| EMDB information | 23785 |
| Descriptor | Ribosomal protein L8, 60S ribosomal protein L11, 60S ribosomal protein L13, ... (84 entities in total) |
| Functional Keywords | 80s mammalian ribosome, translation inhibitor, ribosome |
| Biological source | synthetic construct More |
| Total number of polymer chains | 81 |
| Total formula weight | 3363840.22 |
| Authors | Koga, Y.,Hoang, E.M.,Park, Y.,Keszei, A.F.A.,Murray, J.,Shao, S.,Liau, B.B. (deposition date: 2021-04-06, release date: 2021-09-01, Last modification date: 2024-11-20) |
| Primary citation | Koga, Y.,Hoang, E.M.,Park, Y.,Keszei, A.F.A.,Murray, J.,Shao, S.,Liau, B.B. Discovery of C13-Aminobenzoyl Cycloheximide Derivatives that Potently Inhibit Translation Elongation. J.Am.Chem.Soc., 143:13473-13477, 2021 Cited by PubMed Abstract: Employed for over half a century to study protein synthesis, cycloheximide (CHX, ) is a small molecule natural product that reversibly inhibits translation elongation. More recently, CHX has been applied to ribosome profiling, a method for mapping ribosome positions on mRNA genome-wide. Despite CHX's extensive use, CHX treatment often results in incomplete translation inhibition due to its rapid reversibility, prompting the need for improved reagents. Here, we report the concise synthesis of C13-amide-functionalized CHX derivatives with increased potencies toward protein synthesis inhibition. Cryogenic electron microscopy (cryo-EM) revealed that C13-aminobenzoyl CHX () occupies the same site as CHX, competing with the 3' end of E-site tRNA. We demonstrate that is superior to CHX for ribosome profiling experiments, enabling more effective capture of ribosome conformations through sustained stabilization of polysomes. Our studies identify powerful chemical reagents to study protein synthesis and reveal the molecular basis of their enhanced potency. PubMed: 34403584DOI: 10.1021/jacs.1c05146 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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