7azs | pdb_00007azs

70S thermus thermophilus ribosome with bound antibiotic lead SEQ-569

spinqualitylabelsall models 7azs, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7azs is a 18 chain structure with sequence from Escherichia coli and 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 3.1Å Ligands: 0TD, 2MA, 2MG, 3AU, 4OC, 4SU, 5MC, 5MU, 7MG, K, M2G, MA6, MG, MIA, OHX, OMC, OMG, OMU, PSU, SJH, UR3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL27_THET8 Found on the solvent side of the large subunit.[HAMAP-Rule:MF_00539] Publication Abstract from PubMed The emergence of drug-resistant tuberculosis has created an urgent need for new anti-tubercular agents. Here, we report the discovery of a series of macrolides called sequanamycins with outstanding in vitro and in vivo activity against Mycobacterium tuberculosis (Mtb). Sequanamycins are bacterial ribosome inhibitors that interact with the ribosome in a similar manner to classic macrolides like erythromycin and clarithromycin, but with binding characteristics that allow them to overcome the inherent macrolide resistance of Mtb. Structures of the ribosome with bound inhibitors were used to optimize sequanamycin to produce the advanced lead compound SEQ-9. SEQ-9 was efficacious in mouse models of acute and chronic TB as a single agent, and it demonstrated bactericidal activity in a murine TB infection model in combination with other TB drugs. These results support further investigation of this series as TB clinical candidates, with the potential for use in new regimens against drug-susceptible and drug-resistant TB. Discovery of natural-product-derived sequanamycins as potent oral anti-tuberculosis agents.,Zhang J, Lair C, Roubert C, Amaning K, Barrio MB, Benedetti Y, Cui Z, Xing Z, Li X, Franzblau SG, Baurin N, Bordon-Pallier F, Cantalloube C, Sans S, Silve S, Blanc I, Fraisse L, Rak A, Jenner LB, Yusupova G, Yusupov M, Zhang J, Kaneko T, Yang TJ, Fotouhi N, Nuermberger E, Tyagi S, Betoudji F, Upton A, Sacchettini JC, Lagrange S Cell. 2023 Mar 2;186(5):1013-1025.e24. doi: 10.1016/j.cell.2023.01.043. Epub 2023 , Feb 23. PMID:36827973 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosomal protein THX 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA