8wi9

Structural highlights

Function

RS1_MYCS2 Binds mRNA, facilitating recognition of most mRNAs by the 30S ribosomal subunit during translation initiation (By similarity). Plays a role in trans-translation; binds tmRNA (the product of the ssrA gene) (PubMed:25430994). Binds very poorly to pyrazinoic acid (POA), the active form of the prodrug pyrazinamide (PZA); POA does not disrupt trans-translation in this organism (PubMed:21835980). M.smegmatis is resistant to the antibiotic PZA (PubMed:25430994). In trans-translation Ala-aminoacylated transfer-messenger RNA (tmRNA, product of the ssrA gene; the 2 termini fold to resemble tRNA(Ala) while it encodes a short internal open reading frame (the tag peptide)) acts like a tRNA, entering the A-site of the ribosome and displacing the stalled mRNA (which is subsequently degraded). The ribosome then switches to translate the ORF on the tmRNA, the nascent peptide is terminated with the 'tag peptide' encoded by the tmRNA and thus targeted for degradation.[UniProtKB:P0AG67]^{[1] [2]}

References

1. ↑ Shi W, Zhang X, Jiang X, Yuan H, Lee JS, Barry CE 3rd, Wang H, Zhang W, Zhang Y. Pyrazinamide inhibits trans-translation in Mycobacterium tuberculosis. Science. 2011 Sep 16;333(6049):1630-2. doi: 10.1126/science.1208813. Epub 2011 , Aug 11. PMID:21835980 doi:http://dx.doi.org/10.1126/science.1208813
2. ↑ Yang J, Liu Y, Bi J, Cai Q, Liao X, Li W, Guo C, Zhang Q, Lin T, Zhao Y, Wang H, Liu J, Zhang X, Lin D. Structural basis for targeting the ribosomal protein S1 of Mycobacterium tuberculosis by pyrazinamide. Mol Microbiol. 2015 Mar;95(5):791-803. doi: 10.1111/mmi.12892. Epub 2015 Jan 16. PMID:25430994 doi:http://dx.doi.org/10.1111/mmi.12892