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2hhh
From Proteopedia
Contents |
Crystal structure of kasugamycin bound to the 30S ribosomal subunit
Kasugamycin (Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA. The 3.35-A structure of Ksg bound to the 30S ribosomal subunit presented here provides a structural description of two Ksg-binding sites as well as a basis for understanding Ksg resistance. Notably, neither binding position overlaps with P-site tRNA; instead, Ksg mimics codon nucleotides at the P and E sites by binding within the path of the mRNA. Coupled with biochemical experiments, our results suggest that Ksg indirectly inhibits P-site tRNA binding through perturbation of the mRNA-tRNA codon-anticodon interaction during 30S canonical initiation. In contrast, for 70S-type initiation on leaderless mRNA, the overlap between mRNA and Ksg is reduced and the binding of tRNA is further stabilized by the presence of the 50S subunit, minimizing Ksg efficacy.
The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation., Schluenzen F, Takemoto C, Wilson DN, Kaminishi T, Harms JM, Hanawa-Suetsugu K, Szaflarski W, Kawazoe M, Shirouzu M, Nierhaus KH, Yokoyama S, Fucini P, Nat Struct Mol Biol. 2006 Oct;13(10):871-8. Epub 2006 Sep 24. PMID:16998488
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2hhh is a 21 chain structure with sequence from Thermus thermophilus. Full crystallographic information is available from OCA.
See Also
- Ribosomal protein S10
- Ribosomal protein S11
- Ribosomal protein S12
- Ribosomal protein S13
- Ribosomal protein S14
- Ribosomal protein S15
- Ribosomal protein S16
- Ribosomal protein S17
- Ribosomal protein S18
- Ribosomal protein S19
- Ribosomal protein S2
- Ribosomal protein S20
- Ribosomal protein S3
- Ribosomal protein S4
- Ribosomal protein S5
- Ribosomal protein S6
- Ribosomal protein S7
- Ribosomal protein S8
- Ribosomal protein S9
- Ribosomal protein THX
Reference
- Schluenzen F, Takemoto C, Wilson DN, Kaminishi T, Harms JM, Hanawa-Suetsugu K, Szaflarski W, Kawazoe M, Shirouzu M, Nierhaus KH, Yokoyama S, Fucini P. The antibiotic kasugamycin mimics mRNA nucleotides to destabilize tRNA binding and inhibit canonical translation initiation. Nat Struct Mol Biol. 2006 Oct;13(10):871-8. Epub 2006 Sep 24. PMID:16998488 doi:10.1038/nsmb1145
