Naslov
The aminoglycoside resistance methyltransferase Sgm impedes RsmF methylation at an adjacent rRNA nucleotide in the ribosomal A site

Autori
Čubrilo, Sonja ; Babić, Fedora ; Douthwaite, Stephen ; Maravić Vlahoviček, Gordana

Izvornik
RNA (1355-8382) 15 (2009), 8; 1492-1497

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
aminoglycoside resistance; 16S rRNA methylation; Sgm; YebU (RsmF); RNA mass spectrometry

Sažetak
Ribosome-targeting antibiotics block protein synthesis by binding at functionally important regions of the bacterial rRNA. Resistance is often conferred by addition of a methyl group at the antibiotic binding site within an rRNA region that is already highly modified with several nucleotide methylations. In bacterial rRNA, each methylation requires its own specific methyltransferase enzyme, and this raises the question as to how an extra methyltransferase conferring antibiotic resistance can be accommodated and gain access to its nucleotide target within a short and functionally crowd stretch of the rRNA sequence. Here, we show that the Sgm methyltransferase confers resistance to 4, 6-disubstituted deoxystreptamine aminoglycosides by introducing the 16S rRNA modification m7G1405 within the ribosomal A site. This region of Escherichia coli 16S rRNA already contains several methylated nucleotides including m4Cm1402 and m5C1407. Modification at m5C1407 by the methyltransferase RsmF is impeded as Sgm gains access to its adjacent G1405 target on the 30S ribosomal subunit. An Sgm mutant (G135A), which is impaired in S-adenosylmethionine binding and confers lower resistance, is less able to interfere with RsmF methylation on the 30S subunit. The two methylations at 16S rRNA nucleotide m4Cm1402 are unaffected by both the wild-type and the mutant versions of Sgm. The data indicate that interplay between resistance methyltransferases and the cell’ s own indigenous methyltransferases can play an important role in determining resistance levels.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA