1J5A: Structural Basis For The Interaction Of Antibiotics With The Peptidyl Transferase Center In Eubacteria

Citation:
Abstract
Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design.
PDB ID: 1J5ADownload
MMDB ID: 18796
PDB Deposition Date: 2002/3/6
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Similar Structures:
Biological Unit for 1J5A: tetrameric; determined by author
Molecular Components in 1J5A
Label Count Molecule
Proteins (3 molecules)
1
Ribosomal Protein L4(Gene symbol: rplD)
Molecule annotation
1
Ribosomal Protein L22(Gene symbol: rplV)
Molecule annotation
1
Ribosomal Protein L32(Gene symbol: rpmF)
Molecule annotation
Nucleotide(1 molecule)
1
23S rRNA
Molecule annotation
Chemicals (3 molecules)
1
1
2
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.