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Cited by 68RNA and protein synthesis mechanismsBacterial Genetics and BiotechnologyAntibiotic Resistance in Bacteria

Ribosomal Protection from Tetracycline Mediated by Tet(O): Tet(O) Interaction with Ribosomes Is GTP-Dependent

Trieber, Catharine A., Burkhardt, Nils, Nierhaus, Knud H., Taylor, Diane E.·1998·bchm
DOI 10.1515/bchm.1998.379.7.847
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Abstract

Tet(O) mediates tetracycline resistance by protecting the ribosome from inhibition. A recombinant Tet(O) protein with a histidine tag was purified and its activity in protein synthesis characterized. Tetracycline inhibited the rate of poly(Phe) synthesis, producing short peptide chains. Tet(O)-His was able to restore the elongation rate and processivity. 70S ribosomes bound tetracycline with high affinity. Tet(O)-His in the presence of GTP, but not GDP or GMP, reduced the affinity of the ribosomes for tetracycline. Non-hydrolyzable GTP analogs in the presence of the factor were also able to interfere with tetracycline binding. Ribosomes increased the affinity of Tet(O)-His for GTPgammaS. Tet(O), 70S ribosomes and GTPgammaS formed a complex that could be isolated by gel filtration. The GTP conformer is the active form of Tet(O) that interacts with the ribosome. GTP binding is necessary for Tet(O) activity.

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Crossref · 10.1515/bchm.1998.379.7.847

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33 of 33 references verified0 citation errors · 0 not checkable

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  • In the GDPNP-bound form, Tet(O) was earlier shown biochemically to promote release of Tc from the 70S ribosome.

    “In the GDPNP-bound form Tet(O) was earlier shown biochemically to promote release of Tc from the 70S ribosome 20,22, and the elucidation of the current structure therefore provides direct functional insights into the mechanisms of Tet(O)-mediated Tc resistance.”

    From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [22]

  • Tet(O) and Tet(M) can dislodge tetracycline from the ribosome.

    “Tet(O) and Tet(M) can dislodge tetracycline from the ribosome (6, 54) and, in so doing, increase the apparent dissociation constant ( Kd ) of tetracycline binding to the ribosome from 5 to 30 𝛍 M.”

    From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [54]

  • Tet(O) and Tet(M) increase the apparent dissociation constant of tetracycline binding to the ribosome from 5 to 30 μM.

    “Tet(O) and Tet(M) can dislodge tetracycline from the ribosome (6, 54) and, in so doing, increase the apparent dissociation constant ( Kd ) of tetracycline binding to the ribosome from 5 to 30 𝛍 M.”

    From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [54]

  • The ability of Tet(O) and Tet(M) to dislodge tetracycline is strictly dependent on the presence of GTP.

    “The ability of Tet(O) and Tet(M) to dislodge tetracycline is strictly dependent on the presence of GTP (6, 54), although there is some discrepancy concerning the role of GTP hydrolysis as a nonhydrolyzable GTP analogue was active with Tet(O) (54) but only partially active with Tet(M) (6).”

    From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [54]

  • Binding of Tet(O) in the GTP state is sufficient to trigger the release of tetracycline.

    “Trieber et al. (54) demonstrated that the binding of Tet(O) in the GTP state is sufficient to trigger the release of tetracycline”

    From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [54]

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Authors
Trieber, C. A., Burkhardt, N., Nierhaus, K. H., & Taylor, D. E.
Affiliations
University of Alberta (CA)
ORCID
Venue
bchm
Publisher
Walter de Gruyter GmbH
Published
1998
Volume
379
Issue
7
Pages
847-856
ISSN
  • 1431-6730 (ISSN-L)
  • 1437-4315
DOI
10.1515/bchm.1998.379.7.847
OpenAlex
W2031799761
Cited by
68
References
33
Citations by year
2026: 1 · 2025: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 3 · 2015: 4 · 2014: 7 · 2013: 2 · 2012: 1
FWCI
0.58
Type
journal article
Language
en
Open access
closed
Locations
  • Biological Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords
tetO, tetracycline resistance, ribosome protection, 70S ribosome, GTP binding, GTP gamma S, protein synthesis elongation
MeSH terms
Bacterial Proteins, Carrier Proteins, Guanosine Triphosphate, Histidine, Peptides, Recombinant Fusion Proteins, Ribosomes, Tetracycline, Gene Expression

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