The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.

S M Poulsen, M Karlsson, L B Johansson, B Vester

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2001-Sep
OriginalsprogEngelsk
TidsskriftMolecular Microbiology
Vol/bind41
Udgave nummer5
Sider (fra-til)1091-1099
ISSN0950-382X
StatusUdgivet - 1. sep. 2001

Fingeraftryk

Peptidyl Transferases
RNA
Pharmaceutical Preparations
Transfer RNA
Protein Binding
Peptides
valnemulin
tiamulin

Citer dette

Poulsen, S M ; Karlsson, M ; Johansson, L B ; Vester, B. / The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome. I: Molecular Microbiology. 2001 ; Bind 41, Nr. 5. s. 1091-1099.
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title = "The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.",
abstract = "The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.",
keywords = "Anti-Bacterial Agents, Base Sequence, Binding Sites, DNA Footprinting, Diterpenes, Escherichia coli, Models, Molecular, Molecular Sequence Data, Peptidyl Transferases, RNA, Bacterial, RNA, Ribosomal, 23S, Ribosomes",
author = "Poulsen, {S M} and M Karlsson and Johansson, {L B} and B Vester",
year = "2001",
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Poulsen, SM, Karlsson, M, Johansson, LB & Vester, B 2001, 'The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.', Molecular Microbiology, bind 41, nr. 5, s. 1091-1099.

The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome. / Poulsen, S M; Karlsson, M; Johansson, L B; Vester, B.

I: Molecular Microbiology, Bind 41, Nr. 5, 01.09.2001, s. 1091-1099.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.

AU - Poulsen, S M

AU - Karlsson, M

AU - Johansson, L B

AU - Vester, B

PY - 2001/9/1

Y1 - 2001/9/1

N2 - The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

AB - The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

KW - Anti-Bacterial Agents

KW - Base Sequence

KW - Binding Sites

KW - DNA Footprinting

KW - Diterpenes

KW - Escherichia coli

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Peptidyl Transferases

KW - RNA, Bacterial

KW - RNA, Ribosomal, 23S

KW - Ribosomes

M3 - Journal article

VL - 41

SP - 1091

EP - 1099

JO - Molecular Microbiology

JF - Molecular Microbiology

SN - 0950-382X

IS - 5

ER -