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

Stephen Douthwaite, Lene Jakobsen, Satoko Yoshizawa, Dominique Fourmy

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2008-May-16
OriginalsprogEngelsk
TidsskriftJournal of Molecular Biology
Vol/bind378
Udgave nummer5
Sider (fra-til)969-975
Antal sider6
ISSN0022-2836
DOI
StatusUdgivet - 16. maj 2008

Fingeraftryk

Tylosin
S-Adenosylhomocysteine
S-Adenosylmethionine
Peptides
Enzymes

Citer dette

@article{9eca1490dbff11dd9908000ea68e967b,
title = "Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I",
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.",
keywords = "Anti-Bacterial Agents, Bacterial Proteins, Drug Resistance, Microbial, Methyltransferases, Models, Molecular, Molecular Sequence Data, Nucleic Acid Conformation, Protein Conformation, RNA, Ribosomal, Recombinant Proteins, Tylosin",
author = "Stephen Douthwaite and Lene Jakobsen and Satoko Yoshizawa and Dominique Fourmy",
year = "2008",
month = "5",
day = "16",
doi = "10.1016/j.jmb.2008.03.024",
language = "English",
volume = "378",
pages = "969--975",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Heinemann",
number = "5",

}

Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I. / Douthwaite, Stephen; Jakobsen, Lene; Yoshizawa, Satoko; Fourmy, Dominique.

I: Journal of Molecular Biology, Bind 378, Nr. 5, 16.05.2008, s. 969-975.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Interaction of the tylosin-resistance methyltransferase RlmA II at its rRNA target differs from the orthologue RlmA I

AU - Douthwaite, Stephen

AU - Jakobsen, Lene

AU - Yoshizawa, Satoko

AU - Fourmy, Dominique

PY - 2008/5/16

Y1 - 2008/5/16

N2 - 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.

AB - 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.

KW - Anti-Bacterial Agents

KW - Bacterial Proteins

KW - Drug Resistance, Microbial

KW - Methyltransferases

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Nucleic Acid Conformation

KW - Protein Conformation

KW - RNA, Ribosomal

KW - Recombinant Proteins

KW - Tylosin

U2 - 10.1016/j.jmb.2008.03.024

DO - 10.1016/j.jmb.2008.03.024

M3 - Journal article

C2 - 18406425

VL - 378

SP - 969

EP - 975

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 5

ER -