Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I

Journal of Molecular Biology
Stephen DouthwaiteDominique Fourmy

Abstract

RlmA(II) methylates the N1-position of nucleotide G748 in hairpin 35 of 23 S rRNA. The resultant methyl group extends into the peptide channel of the 50 S ribosomal subunit and confers resistance to tylosin and other mycinosylated macrolide antibiotics. Methylation at G748 occurs in several groups of Gram-positive bacteria, including the tylosin-producer Streptomyces fradiae and the pathogen Streptococcus pneumoniae. Recombinant S. pneumoniae RlmA(II) was purified and shown to retain its activity and specificity in vitro when tested on unmethylated 23 S rRNA substrates. RlmA(II) makes multiple footprint contacts with nucleotides in stem-loops 33, 34 and 35, and does not interact elsewhere in the rRNA. Binding of RlmA(II) to the rRNA is dependent on the cofactor S-adenosylmethionine (or S-adenosylhomocysteine). RlmA(II) interacts with the same rRNA region as the orthologous enzyme RlmA(I) that methylates at nucleotide G745. Differences in nucleotide contacts within hairpin 35 indicate how the two methyltransferases recognize their distinct targets.

References

Jan 1, 1984·Annual Review of Biochemistry·H F Noller
Jul 13, 2002·Trends in Biochemical Sciences·Wayne A Decatur, Maurille J Fournier
Aug 2, 2002·Molecular Cell·Jeffrey L HansenThomas A Steitz
Nov 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Mingfu Liu, Stephen Douthwaite
Mar 8, 2003·Structure·Frank SchlünzenAda Yonath
Mar 18, 2003·Journal of Cell Science·Jörg M HarmsAda Yonath
Mar 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kalyan DasGaetano T Montelione
Oct 1, 2005·Molecular Microbiology·Stephen DouthwaiteLene Jakobsen
Nov 8, 2005·Science·Barbara S SchuwirthJamie H Doudna Cate
Sep 9, 2006·Science·Maria SelmerV Ramakrishnan
Aug 4, 2007·Journal of Molecular Biology·Isabelle LebarsDominique Fourmy

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Citations

Jul 3, 2010·Proteins·Sarel J FleishmanDavid Baker
May 9, 2012·Wiley Interdisciplinary Reviews. RNA·Dominique Fourmy, Satoko Yoshizawa

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