1xbp
From Proteopedia
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Inhibition of peptide bond formation by pleuromutilins: The structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with Tiamulin
Overview
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.
About this Structure
1XBP is a Protein complex structure of sequences from Deinococcus radiodurans with MUL as ligand. Full crystallographic information is available from OCA.
Reference
Inhibition of peptide bond formation by pleuromutilins: the structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with tiamulin., Schlunzen F, Pyetan E, Fucini P, Yonath A, Harms JM, Mol Microbiol. 2004 Dec;54(5):1287-94. PMID:15554968
Page seeded by OCA on Wed Nov 21 05:58:01 2007
