Mechanism of Tet(O)‐mediated tetracycline resistance
Open accessAbstract
Tet(O) is an elongation factor-like protein which confers resistance to the protein synthesis inhibitor tetracycline by promoting the release of the drug from its inhibitory site on the ribosome. Here we investigated the interaction of Tet(O) with the elongating ribosome and show, using dimethyl sulfate (DMS) probing and binding assays, that it interacts preferentially with the post-translocational ribosome. Furthermore, using an XTP-dependent mutant of Tet(O), we demonstrated that Tet(O) induces conformational rearrangements within the ribosome which can be detected by EF-Tu, and manifested as a stimulation in the GTPase activity of this elongation factor. As such, these conformational changes probably involve the ribosomal GTPase-associated center and, accordingly, Tet(O) alters the DMS modification pattern of the L11 region. Additionally, tetracycline binding is associated with an E(a) of 58 kJ/mol. These results suggest a model where both Tet(O) and tetracycline induce a conformational change in functionally opposite directions and the Tet(O)-induced conformation persists after it has left the ribosome; this prevents rebinding of the drug while allowing productive A-site occupation by a ternary complex in the presence of tetracycline.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tet(O) protects the bacterial ribosome from binding the antibiotic tetracycline.
“Tetracycline resistance protein Tet(O), which protects the bacterial ribosome from binding the antibiotic tetracycline, is a translational GTPase with significant similarity in both sequence and structure to the elongation factor EF-G.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [8]
Tet(M) and Tet(O) are paralogs of the translational GTPase EF-G and actively remove Tc from the ribosome in a GTP-hydrolysis-dependent fashion.
“Several of these proteins–the best-known being Tet(M) and Tet(O) – are paralogs of the translational GTPase EF-G 6 and actively remove Tc from the ribosome in a GTP-hydrolysis-dependent fashion 7,8.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [8]
The corridor acts as the only pathway for the dissociating Tc molecule's release from the ribosome.
“The dissociating Tc molecule has to navigate this corridor, which acts as the only pathway for the molecule’s release from the ribosome, which might explain the high activation energy of the process 8.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [8]
The corridor might explain the high activation energy of the Tc release process.
“The dissociating Tc molecule has to navigate this corridor, which acts as the only pathway for the molecule’s release from the ribosome, which might explain the high activation energy of the process 8.”
From Mechanism of tetracycline resistance by ribosomal protection protein Tet(O) (2013) · cites this paper as [8]
A tetracycline-induced conformational change in the ribosome may promote Tet(O) binding.
“First, a tetracycline-induced conformational change in the ribosome may promote Tet(O) binding (11).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
Tet(O) cannot bind a ribosome with an occupied A site.
“Tet(O) cannot bind a ribosome with an occupied A site (11).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
In the presence of tetracycline, the ribosome is blocked with an open A site, providing a kinetic window for Tet(O) to act and distinguishing the tetracycline-blocked ribosome from a translating ribosome.
“In the presence of tetracycline, the ribosome is blocked with an open A site and this could provide a kinetic window for Tet(O) to act, thus distinguishing the tetracycline-blocked ribosome from a translating ribosome (11).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
A ribosome with an open A site is the preferred substrate for Tet(O).
“a ribosome in this condition seems to be the preferred substrate for Tet(O)”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
Tet(O) can stimulate the GTPase activity of EF-Tu.
“the fact that Tet(O) can stimulate the GTPase activity of EF-Tu”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
A conformational change can be inferred from several biochemical experiments.
“a conformational change can be inferred from several biochemical experiments (11, 14, 32, 56).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
Tet(O) can induce conformational changes in the ribosome that persist after it has dissociated.
“suggests that Tet(O) can induce conformational changes in the ribosome that persist after it has dissociated (11).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
When biochemical and structural data describing the RPP's ribosomal binding site are combined, the interaction of the RPP with the ribosome can be modeled with high precision.
“When the biochemical (11, 12, 15) and structural (45) data describing the RPP's ribosomal binding site are combined, the interaction of the RPP with the ribosome can be modeled with high precision (Table 1).”
From Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance (2003) · cites this paper as [11]
The conformational changes were proposed to persist after TetO has dissociated from the ribosome, preventing rebinding of tetracycline as well as stimulating delivery of the ternary complex.
“Moreover, the conformational changes were proposed to persist after TetO has dissociated from the ribosome, preventing rebinding of tetracycline as well as stimulating delivery of the ternary complex (9,16).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [16]
The structural features imparted by TetM on the ribosome would contribute to the synergistic effect that TetM has been proposed to have on EF-Tu binding to the ribosome.
“Collectively, we believe these structural features imparted by TetM on the ribosome would contribute to the synergistic effect that TetM has been proposed to have on EF-Tu binding to the ribosome (16).”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [16]
The flipped-out conformation of A1492 and A1493 persists upon dissociation of TetM from the ribosome, which promotes binding of the ternary complex.
“Footprinting experiments suggest that the flipped-out conformation of A1492 and A1493 persists upon dissociation of TetM from the ribosome (16), which promote binding of the ternary complex.”
From Structural basis for TetM-mediated tetracycline resistance (2012) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Chopra, I., & Roberts, M. (2001) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.65.2.232-260.2001 · Cited by 4,517 · see citing works
Cannone, J. J., Subramanian, S., Schnare, M. N., Collett, J. R., D'Souza, L. M., Du, Y., Feng, B. Y., Lin, N., Madabusi, L. V., Müller, K. M., et al. (2002) · BMC Bioinformatics · doi:10.1186/1471-2105-3-2 · Cited by 1,614 · see citing works
Interaction of antibiotics with functional sites in 16S ribosomal RNA
Moazed, D., & Noller, H. F. (1987) · Nature · doi:10.1038/327389a0 · Cited by 1,150 · see citing works
Classification and evolution of P-loop GTPases and related ATPases
Leipe, D. D., Wolf, Y. I., Koonin, E. V., & Aravind, L. (2002) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.5378 · Cited by 1,148 · see citing works
Brodersen, D. E., Clemons, W. M., Carter, A. P., Morgan-Warren, R. J., Wimberly, B. T., & Ramakrishnan, V. (2000) · Cell · doi:10.1016/s0092-8674(00)00216-6 · Cited by 950 · see citing works
Mead, D. A., Szczesna-Skorupa, E., & KEMPER, B. W. (1986) · Protein Engineering Design and Selection · doi:10.1093/protein/1.1.67 · Cited by 816 · see citing works
Carson, M. (1991) · Journal of Applied Crystallography · doi:10.1107/s0021889891007240 · Cited by 809 · see citing works
Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3
Pioletti, M., Schlünzen, F., Harms, J., Zarivach, R., Glühmann, M., Avila, H., Bashan, A., Bartels, H., Auerbach, T., Jacobi, C., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.8.1829 · Cited by 527 · see citing works
Interaction of elongation factors EF-G and EF-Tu with a conserved loop in 23S RNA
Moazed, D., Robertson, J., & Noller, H. F. (1988) · Nature · doi:10.1038/334362a0 · Cited by 486 · see citing works
[33] Structural analysis of RNA using chemical and enzymatic probing monitored by primer extension
Stern, S., Moazed, D., & Noller, H. F. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(88)64064-x · Cited by 429 · see citing works
Solution Structure of the E. coli 70S Ribosome at 11.5 Å Resolution
Gabashvili, I. S., Agrawal, R. K., Spahn, C. M. T., Grassucci, R. A., Svergun, D. I., Frank, J., & Penczek, P. A. (2000) · Cell · doi:10.1016/s0092-8674(00)80690-x · Cited by 405 · see citing works
Visualization of elongation factor Tu on the Escherichia coli ribosome
Stark, H., Rodnina, M. V., Rinke-Appel, J., Brimacombe, R. L. C., Wintermeyer, W., & van Heel, M. (1997) · Nature · doi:10.1038/38770 · Cited by 347 · see citing works
A Detailed View of a Ribosomal Active Site
Wimberly, B. T., Guymon, R., McCutcheon, J. P., White, S. W., & Ramakrishnan, V. (1999) · Cell · doi:10.1016/s0092-8674(00)80759-x · Cited by 331 · see citing works
Endo, Y., & Wool, I. G. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)34241-8 · Cited by 304 · see citing works
Cryo‐EM reveals an active role for aminoacyl‐tRNA in the accommodation process
Valle, M., Sengupta, J., Swami, N. K., Grassucci, R. A., Burkhardt, N., Nierhaus, K. H., Agrawal, R. K., & Frank, J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf326 · Cited by 296 · see citing works
Self-citationBlaha, G. M., Stelzl, U., Spahn, C. M. T., Agrawal, R. K., Frank, J., & Nierhaus, K. H. (2000) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(00)17021-1 · Cited by 215 · see citing works
Self-citationRibotoxin recognition of ribosomal RNA and a proposal for the mechanism of translocation
Wool, I. G., Glück, A., & Endo, Y. (1992) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(92)90407-z · Cited by 194 · see citing works
Hausner, T. P., Atmadja, J., & Nierhaus, K. H. (1987) · Biochimie · doi:10.1016/0300-9084(87)90225-2 · Cited by 180 · see citing works
Self-citationA mutation that alters the nucleotide specificity of elongation factor Tu, a GTP regulatory protein.
Hwang, Y., & Miller, D. L. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45170-8 · Cited by 152 · see citing works
Burdett, V (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)49928-0 · Cited by 141 · see citing works
Rheinberger, H., Geigenmüller, U., Wedde, M., & Nierhaus, K. H. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(88)64076-6 · Cited by 131 · see citing works
Self-citationKinetics for the life sciences: receptors, transmitters and catalysts
(1996) · Choice Reviews Online · doi:10.5860/choice.33-5084 · Cited by 123 · see citing works
Tet(M)-promoted release of tetracycline from ribosomes is GTP dependent
Burdett, V (1996) · Journal of Bacteriology · doi:10.1128/jb.178.11.3246-3251.1996 · Cited by 121 · see citing works
Toward a Model for the Interaction Between Elongation Factor Tu and the Ribosome
Weijland, A., & Parmeggiani, A. (1993) · Science · doi:10.1126/science.8446899 · Cited by 118 · see citing works
Porse, B. T., Leviev, I., Mankin, A. S., & Garrett, R. A. (1998) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1541 · Cited by 114 · see citing works
Thiostrepton: A ribosomal inhibitor of translocation
Pestka, S. (1970) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(70)90956-3 · Cited by 103 · see citing works
Cameron, D. M., Thompson, J., March, P. E., & Dahlberg, A. E. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00235-8 · Cited by 99 · see citing works
Effects of some proteins that inactivate the eukaryotic ribosome
Fernández-Puentes, C., & Vázquez, D. (1977) · FEBS Letters · doi:10.1016/0014-5793(77)80292-5 · Cited by 98 · see citing works
Allosteric interactions between the ribosomal transfer RNA-binding sites A and E.
Rheinberger, H., & Nierhaus, K. H. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67628-8 · Cited by 88 · see citing works
Self-citationSanchez-Pescador, R., Brown, J. T., Roberts, M., & Urdea, M. S. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.3.1218 · Cited by 87 · see citing works
Ribosome-tetracycline interactions
Tritton, T. R. (1977) · Biochemistry · doi:10.1021/bi00637a029 · Cited by 86 · see citing works
Spahn, C. M. T., Blaha, G., Agrawal, R. K., Penczek, P., Grassucci, R. A., Trieber, C. A., Connell, S. R., Taylor, D. E., Nierhaus, K. H., & Frank, J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00238-6 · Cited by 81 · see citing works
Self-citationDasmahapatra, B., & Chakraburtty, K. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68730-2 · Cited by 77 · see citing works
Schilling-Bartetzko, S., Bartetzko, A., & Nierhaus, K. H. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42890-6 · Cited by 76 · see citing works
Self-citationMolecular studies on the mechanism of tetracycline resistance mediated by Tet(O)
Manavathu, E. K., Fernandez, C. L., Cooperman, B. S., & Taylor, D. E. (1990) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.34.1.71 · Cited by 72 · see citing works
Self-citationTrieber, C. A., Burkhardt, N., Nierhaus, K. H., & Taylor, D. E. (1998) · bchm · doi:10.1515/bchm.1998.379.7.847 · Cited by 68 · see citing works
Self-citationChakraburtty, K., & Kamath, A. (1988) · International Journal of Biochemistry · doi:10.1016/0020-711x(88)90096-1 · Cited by 65 · see citing works
Bodley, J. W., Lin, L., & Highland, J. H. (1970) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(70)90543-7 · Cited by 64 · see citing works
Bommer, U. A., Burkhardt, N., Jünemann, R., et al. (1997) · doi:10.1093/oso/9780199634958.003.0009 · Cited by 52 · see citing works
Synergism between the GTPase Activities of EF-Tu·GTP and EF-G·GTP on Empty Ribosomes
Mesters, J. R., Potapov, A. P., de Graaf, J. M., & Kraal, B. (1994) · Journal of Molecular Biology · doi:10.1006/jmbi.1994.1614 · Cited by 50 · see citing works
Noah, J. W., Dolan, M. A., Babin, P., & Wollenzien, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.23.16576 · Cited by 46 · see citing works
Continuum Electrostatic Methods Applied to pH-Dependent Properties of Antibody–Antigen Association
Gibas, C., Jambeck, P., & Subramaniam, S. (2000) · Methods · doi:10.1006/meth.1999.0923 · Cited by 45 · see citing works
Connell, S. R., Trieber, C. A., Stelzl, U., Einfeldt, E., Taylor, D. E., & Nierhaus, K. H. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03115.x · Cited by 42 · see citing works
Self-citationWeijland, A., Parlato, G., & Parmeggiani, A. (1994) · Biochemistry · doi:10.1021/bi00201a019 · Cited by 39 · see citing works
Binding Interaction between Tet(M) and the Ribosome: Requirements for Binding
Dantley, K. A., Dannelly, H. K., & Burdett, V. (1998) · Journal of Bacteriology · doi:10.1128/jb.180.16.4089-4092.1998 · Cited by 37 · see citing works
Wang, Y., & Taylor, D. E. (1991) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.35.10.2020 · Cited by 34 · see citing works
Self-citationDahlberg, A. E., Lund, E., Kjeldgaard, N. O., Bowman, C. M., & Nomura, M. (1973) · Biochemistry · doi:10.1021/bi00729a025 · Cited by 28 · see citing works
Nierhaus, K. H., Schilling-Bartetzko, S., & Twardowski, T. (1992) · Biochimie · doi:10.1016/0300-9084(92)90118-x · Cited by 27 · see citing works
Self-citationPeriodic Conformational Changes in rRNA
Polacek, N., Patzke, S., Nierhaus, K. H., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(05)00009-2 · Cited by 23 · see citing works
Self-citationKinetics for the life sciences: Receptors, transmitters and catalysts
(1996) · General Pharmacology The Vascular System · doi:10.1016/s0306-3623(96)90032-4 · Cited by 21 · see citing works
Cryo-EM reveals an active role for aminoacyl-tRNA in the accommodation process
Valle, M., Sengupta, J., Swami, N. K., et al. (2018) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789813234864_0029 · Cited by 20 · see citing works
Bodley, J. W., OʼDea, R. F., Gordon, J., et al. (1971) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)62173-8 · Cited by 18 · see citing works
Grewal, J., Manavathu, E. K., & Taylor, D. E. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.12.2645 · Cited by 16 · see citing works
Self-citationPeriodic Conformational Changes in rRNAMonitoring the Dynamics of Translating Ribosomes
Polacek, N. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00017-4 · Cited by 14 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Graham,J. and Rickwood,D. (eds), Subcellular Fractionation. A Practical Approach. IRL Press at Oxford University Press, Oxford, UK, pp. 271±301.
Cited by
Sorted by citations
Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance
Connell, S. R., Tracz, D. M., Nierhaus, K. H., & Taylor, D. E. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.12.3675-3681.2003 · Cited by 449 · see citing works
Self-citationThe bacterial translation stress response.
Starosta, A. L., Lassak, J., Jung, K., & Wilson, D. N. (2014) · FEMS Microbiology Reviews · doi:10.1111/1574-6976.12083 · Cited by 210 · see citing works
Structural basis for TetM-mediated tetracycline resistance
Dönhöfer, A., Franckenberg, S., Wickles, S., Berninghausen, O., Beckmann, R., & Wilson, D. N. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208037109 · Cited by 217 · see citing works
Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic
Grossman, T. H., Starosta, A. L., Fyfe, C., O'Brien, W., Rothstein, D. M., Mikolajka, A., Wilson, D. N., & Sutcliffe, J. A. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06187-11 · Cited by 162 · see citing works
Mechanism of tetracycline resistance by ribosomal protection protein Tet(O)
Li, W., Atkinson, G. C., Thakor, N. S., Allas, Ü., Lu, C.-C., Chan, K.-Y., Tenson, T., Schulten, K., Wilson, K. S., Hauryliuk, V., et al. (2013) · Nature Communications · doi:10.1038/ncomms2470 · Cited by 147 · see citing works
Phylogenetic distribution of translational GTPases in bacteria
Margus, T., Remm, M., & Tenson, T. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-15 · Cited by 115 · see citing works
Chimeras of bacterial translation factors Tet(O) and EF‐G
Thakor, N. S., Nechifor, R., Scott, P. G., Keelan, M., Taylor, D. E., & Wilson, K. S. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.03.023 · Cited by 4 · see citing works
Self-citation
- Authors
- Connell, S. R., Trieber, C. A., Dinos, G. P., Einfeldt, E., Taylor, D. E., & Nierhaus, K. H.
- Affiliations
- Max Planck Society (DE)
- University of Alberta (CA)
- Corresponding author
- Nierhaus, Knud H.
- Venue
- The EMBO Journal
- Published
- 2003-02-17
- Volume
- 22
- Issue
- 4
- Pages
- 945-953
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC145453
- OpenAlex
- W2107825969
- Cited by
- 127
- References
- 54
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 4 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 9 · 2017: 7 · 2016: 8 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 1.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Alberta Heritage Foundation for Medical Research
- Natural Sciences and Engineering Research Council of Canada
- 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, ribosome recycling, protein synthesis inhibition, ternary complex
- MeSH terms
- Bacterial Proteins, Carrier Proteins, Protein Synthesis Inhibitors, Ribosomes, Temperature, Tetracycline, Campylobacter jejuni, Peptide Elongation Factor 2, Drug Resistance, Bacterial
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
