1XBP

Inhibition of peptide bond formation by pleuromutilins: The structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with Tiamulin

Summary for 1XBP

• Entry DOI: 10.2210/pdb1xbp/pdb
• Related: 1NKW
• Descriptor: 23S RIBOSOMAL RNA, 50S ribosomal protein L13, 50S ribosomal protein L14, ... (32 entities in total)
• Functional Keywords: tiamulin, pleuromutilin, 50s ribosome, ribosome
• Biological source: Deinococcus radiodurans; More
• Total number of polymer chains: 31
• Total formula weight: 1380156.09

Authors

Schluenzen, F.,Pyetan, E.,Fucini, P.,Yonath, A.,Harms, J.M. (deposition date: 2004-08-31, release date: 2005-03-01, Last modification date: 2023-08-23)

Primary citation

Schluenzen, F.,Pyetan, E.,Fucini, P.,Yonath, A.,Harms, J.M.
Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin.
Mol.Microbiol., 54:1287-1294, 2004

PubMed Abstract: Tiamulin, a prominent member of the pleuromutilin class of antibiotics, is a potent inhibitor of protein synthesis in bacteria. Up to now the effect of pleuromutilins on the ribosome has not been determined on a molecular level. The 3.5 A structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin provides for the first time a detailed picture of its interactions with the 23S rRNA, thus explaining the molecular mechanism of the antimicrobial activity of the pleuromutilin class of antibiotics. Our results show that tiamulin is located within the peptidyl transferase center (PTC) of the 50S ribosomal subunit with its tricyclic mutilin core positioned in a tight pocket at the A-tRNA binding site. Also, the extension, which protrudes from its mutilin core, partially overlaps with the P-tRNA binding site. Thereby, tiamulin directly inhibits peptide bond formation. Comparison of the tiamulin binding site with other PTC targeting drugs, like chloramphenicol, clindamycin and streptogramins, may facilitate the design of modified or hybridized drugs that extend the applicability of this class of antibiotics.

PubMed: 15554968
DOI: 10.1111/j.1365-2958.2004.04346.x

Experimental method

X-RAY DIFFRACTION (3.5 Å)