Insights into the decoding mechanism from recent ribosome structures

Ogle, J.M.; Carter, Andrew P.; Ramakrishnan, V.

doi:10.1016/s0968-0004(03)00066-5

Cited by 351 publications

(372 citation statements)

References 44 publications

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“…In this asymmetric internal loop, two universally conserved adenine residues, A1492 and A1493, are directly involved in the decoding process, during which they flip out of the helix to analyze the codon–anticodon complex 108. The energy needed for this flip is thought to be compensated by stabilizing interactions between the nucleotides and the codon–anticodon complex, but only in the case of a cognate tRNA.…”

Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

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Section: Protein Synthesis Inhibitorsmentioning

confidence: 99%

Targeting Antibiotic Resistance

2016

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“…Consequently a variety of quality control strategies are employed by the cell to ensure that typically only about one in every 10 4 codons is mistranslated, even though significantly higher rates at particular codons can be tolerated (Ruusala et al 1982;Kurland 1992;Min et al 2003;Nú ñ ez et al 2004). Aside from codon-anticodon pairing (Ogle et al 2003), the mechanisms of translational quality control are broadly of three types; specificity of substrate selection by aa-tRNA synthetases, proofreading, and exclusion from the ribosome. Exhaustive studies over the last four decades have described in intricate detail the molecular recognition strategies that allow synthetases to select from the cellular pool particular canonical amino acids and tRNAs to generate correctly matched aa-tRNAs (for review, see .…”

Section: Quality Control and Aa-trnamentioning

confidence: 99%

Aminoacyl-tRNAs: setting the limits of the genetic code

Ibba¹,

Söll²

2004

Genes Dev.

153

117

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Aminoacyl-tRNAs (aa-tRNAs) are simple molecules with a single purpose-to serve as substrates for translation. They consist of mature tRNAs to which an amino acid has been esterified at the 3Ј-end. The 20 different types of aa-tRNA are made by the 20 different aminoacyl-tRNA synthetases (aaRSs, of which there are two classes), one for each amino acid of the genetic code . This would be fine if it were not for the fact that such a straightforward textbook scenario is not true in a single known living organism. aa-tRNAs lie at the heart of gene expression; they interpret the genetic code by providing the interface between nucleic acid triplets in mRNA and the corresponding amino acids in proteins. The synthesis of aa-tRNAs impacts the accuracy of translation, the expansion of the genetic code, and even provides tangible links to primary metabolism. These central roles vest immense power in aa-tRNAs, and recent studies show just how complex and diverse their synthesis is.

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“…The other extreme viewpoint is known as induced fit, in which formation of the correct bound conformation is facilitated by the presence of the binding partner, as originally proposed by Koshland. 11 Such a mechanism has been inferred for the recognition and proof-reading of tRNA by the ribosome [12][13][14] and for the open/closed transition of polymerases. 15 In the case of intrinsically disordered proteins (IDPs), which often adopt specific structures upon binding to other proteins or nucleic acids, 16,17 one may ask whether the bound conformation of the IDP must be adopted prior to binding, or must be induced by the binding partner.…”

Section: Introductionmentioning

confidence: 99%

Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

Knott

Best

2014

The Journal of Chemical Physics

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Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an "induced fit" or "conformational selection" mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD. © 2014 AIP Publishing LLC.

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Insights into the decoding mechanism from recent ribosome structures

Cited by 351 publications

References 44 publications

Targeting Antibiotic Resistance

Targeting Antibiotic Resistance

Aminoacyl-tRNAs: setting the limits of the genetic code

Discriminating binding mechanisms of an intrinsically disordered protein via a multi-state coarse-grained model

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