Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance

Connell, Sean R.; Tracz, Dobryan M.; Nierhaus, Knud H.; Taylor, Diane E.

doi:10.1128/aac.47.12.3675-3681.2003

Cited by 378 publications

(291 citation statements)

References 57 publications

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“…This has been proposed to be brought about via TetM-induced conformational changes within the ribosome that prevent tetracycline rebinding, and yet promote binding of the ternary complex EF-Tu•GTP•aa-tRNA (9,15,16). Indeed, our findings provide structural support for this model, as the conformation of C1054 and U1196 in the TetM•70S structure appears to be most compatible with binding of EF-Tu•GTP•aa-tRNA (Fig.…”

Section: Resultssupporting

confidence: 63%

“…Ribosome protection is mediated by so-called ribosome protection proteins (RPPs), with the most prevalent and best characterized being TetO and TetM (5,9). TetO and TetM exhibit ∼75% sequence similarity with each other (10) and ∼45% similarity with elongation factor G (EF-G) (SI Appendix, Fig.…”

mentioning

confidence: 99%

“…As TetO is not observed to directly interact with C1054 or A1408 (14), TetO was suggested to chase tetracycline from the ribosome indirectly via inducing local disturbances within h34 (9,14,15). 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).…”

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confidence: 99%

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Structural basis for TetM-mediated tetracycline resistance

Dönhöfer

Franckenberg

Wickles

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

165

141

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Ribosome protection proteins (RPPs) confer tetracycline resistance by binding to the ribosome and chasing the drug from its binding site. The current model for the mechanism of action of RPPs proposes that drug release is indirect and achieved via conformational changes within the drug-binding site induced upon binding of the RPP to the ribosome. Here we report a cryo-EM structure of the RPP TetM in complex with the 70S ribosome at 7.2-Å resolution. The structure reveals the contacts of TetM with the ribosome, including interaction between the conserved and functionally critical C-terminal extension of TetM and the decoding center of the small subunit. Moreover, we observe direct interaction between domain IV of TetM and the tetracycline binding site and identify residues critical for conferring tetracycline resistance. A model is presented whereby TetM directly dislodges tetracycline to confer resistance.antibiotic | protein synthesis | RNA | tigecycline | translation

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Section: Resultssupporting

confidence: 63%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structural basis for TetM-mediated tetracycline resistance

Dönhöfer

Franckenberg

Wickles

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

165

141

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“…Similar to the toxic mechanism of aminoglycosides, tetracyclines can impair the function of mitochondrial ribosomes (Fig. 2) [149,150].…”

Section: Aminoglycosides and Tetracyclinesmentioning

confidence: 94%

Drug-induced acid-base disorders

et al. 2014

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The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g

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“…As the development of science and technology, there was strong development in the medicine for treating the diseases using chemical moieties 9,10 . Their use in medicine increased the life span of the humans but increases the different side effects and the diseases causing microorganisms are getting resistance, this leading to the development of new diseases like Zika fever, swine flu etc [11][12][13] . So, there is a growing interest in pharmacological evolution of various unknown plants used in traditional medicine around the world including India 14 .…”

Section: Introductionmentioning

confidence: 99%

Anti-Tubercular Activity of Oxystelma Esculantum

Srikanth¹,

Prasadarao²,

Badrinath³

et al. 2017

Int. Res. J. Pharm.

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Oxystelma esculentum is one of the traditional medicinal plant which have been using in treatment of different diseases with less scientific evidence belongs to the family Ascelepiadaceae. In this point of view, the present work carried out to evaluate its anti-tuberculosis, which is the most mortality causing diseases around the world. The qualitative phytochemical analysis was carried out by standard protocols and anti-tuberculosis activity was carried out using Microplate Alamar Blue Assay method on Mycobacterium tuberculosis reference strain H37Rv. The ethanolic extract of O. esculentum flowers showed the positive results for the sterols, phenols, alkaloids, flavonoids, glycosides, tannins and carbohydrates and gave negative result for terpenoids, saponins and oils. The MIC of the extracts which showed inhibitory effect on M. tuberculosis H37Rv was determined at various concentrations of 1, 6.125, 12.5, 25, 50, 100 mg/ml. Accordingly, the MIC of Ethanolic and Aqueous extract O. esculentum in ethanol and water of were 1 mg/ml and 1 mg/ml respectively. So, the present study supports its medicinal u se and further studies on isolation of particular bioactive compounds from O. esculentum are useful.

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Ribosomal Protection Proteins and Their Mechanism ofTetracyclineResistance

Cited by 378 publications

References 57 publications

Structural basis for TetM-mediated tetracycline resistance

Structural basis for TetM-mediated tetracycline resistance

Drug-induced acid-base disorders

Anti-Tubercular Activity of Oxystelma Esculantum

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