3OHC: Structure Of The Thermus Thermophilus Ribosome Complexed With Erythromycin

Citation:
Abstract
The increasing prevalence of antibiotic-resistant pathogens reinforces the need for structures of antibiotic-ribosome complexes that are accurate enough to enable the rational design of novel ribosome-targeting therapeutics. Structures of many antibiotics in complex with both archaeal and eubacterial ribosomes have been determined, yet discrepancies between several of these models have raised the question of whether these differences arise from species-specific variations or from experimental problems. Our structure of chloramphenicol in complex with the 70S ribosome from Thermus thermophilus suggests a model for chloramphenicol bound to the large subunit of the bacterial ribosome that is radically different from the prevailing model. Further, our structures of the macrolide antibiotics erythromycin and azithromycin in complex with a bacterial ribosome are indistinguishable from those determined of complexes with the 50S subunit of Haloarcula marismortui, but differ significantly from the models that have been published for 50S subunit complexes of the eubacterium Deinococcus radiodurans. Our structure of the antibiotic telithromycin bound to the T. thermophilus ribosome reveals a lactone ring with a conformation similar to that observed in the H. marismortui and D. radiodurans complexes. However, the alkyl-aryl moiety is oriented differently in all three organisms, and the contacts observed with the T. thermophilus ribosome are consistent with biochemical studies performed on the Escherichia coli ribosome. Thus, our results support a mode of macrolide binding that is largely conserved across species, suggesting that the quality and interpretation of electron density, rather than species specificity, may be responsible for many of the discrepancies between the models.
MMDB ID: 99527
PDB Deposition Date: 2010/8/17
Updated in MMDB: 2012/08
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Merged PDB IDs:3OHC 3OHD 3OHJ 3OHK
Asymmetric Unit for 3OHC: 102-meric
Molecular Components in 3OHC
Label Count Molecule
Proteins (96 molecules)
2
30S Ribosomal Protein S2
Molecule annotation
2
30S Ribosomal Protein S3
Molecule annotation
2
30S Ribosomal Protein S4
Molecule annotation
2
30S Ribosomal Protein S5
Molecule annotation
2
30S Ribosomal Protein S6
Molecule annotation
2
30S Ribosomal Protein S7
Molecule annotation
2
30S Ribosomal Protein S8
Molecule annotation
2
30S Ribosomal Protein S9
Molecule annotation
2
30S Ribosomal Protein S10
Molecule annotation
2
30S Ribosomal Protein S11
Molecule annotation
2
30S Ribosomal Protein S12
Molecule annotation
2
30S Ribosomal Protein S13
Molecule annotation
2
30S Ribosomal Protein S14
Molecule annotation
2
30S Ribosomal Protein S15
Molecule annotation
2
30S Ribosomal Protein S16
Molecule annotation
2
30S Ribosomal Protein S17
Molecule annotation
2
30S Ribosomal Protein S18
Molecule annotation
2
30S Ribosomal Protein S19
Molecule annotation
2
30S Ribosomal Protein S20
Molecule annotation
2
30S Ribosomal Protein THX
Molecule annotation
2
50S Ribosomal Protein L27
Molecule annotation
2
50S Ribosomal Protein L28
Molecule annotation
2
50S Ribosomal Protein L29
Molecule annotation
2
50S Ribosomal Protein L30
Molecule annotation
2
50S Ribosomal Protein L31
Molecule annotation
2
50S Ribosomal Protein L32
Molecule annotation
2
50S Ribosomal Protein L33
Molecule annotation
2
50S Ribosomal Protein L34
Molecule annotation
2
50S Ribosomal Protein L35
Molecule annotation
2
50S Ribosomal Protein L2
Molecule annotation
2
50S Ribosomal Protein L3
Molecule annotation
2
50S Ribosomal Protein L4
Molecule annotation
2
50S Ribosomal Protein L5
Molecule annotation
2
50S Ribosomal Protein L6
Molecule annotation
2
50S Ribosomal Protein L9
Molecule annotation
2
50S Ribosomal Protein L13
Molecule annotation
2
50S Ribosomal Protein L14
Molecule annotation
2
50S Ribosomal Protein L15
Molecule annotation
2
50S Ribosomal Protein L16
Molecule annotation
2
50S Ribosomal Protein L17
Molecule annotation
2
50S Ribosomal Protein L18
Molecule annotation
2
50S Ribosomal Protein L19
Molecule annotation
2
50S Ribosomal Protein L20
Molecule annotation
2
50S Ribosomal Protein L21
Molecule annotation
2
50S Ribosomal Protein L22
Molecule annotation
2
50S Ribosomal Protein L23
Molecule annotation
2
50S Ribosomal Protein L24
Molecule annotation
2
50S Ribosomal Protein L25
Molecule annotation
Nucleotides(3 molecules)
2
16S rRNA
Molecule annotation
2
23S Ribosomal RNA
Molecule annotation
2
5S Ribosomal RNA
Molecule annotation
Chemicals (838 molecules)
1
830
Molecule information is not avaliable.
2
4
Molecule information is not avaliable.
3
2
Molecule information is not avaliable.
4
2
Molecule information is not avaliable.
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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