RNA Affinity for Molecular L-Histidine; Genetic Code Origins

Majerfeld, Irene; Puthenvedu, Deepa; Yarus, Michael

doi:10.1007/s00239-004-0360-9

Cited by 60 publications

(52 citation statements)

References 23 publications

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“…The lengths of the DOPPs 1 and 2 are identical, with the only difference being the presence of two enantiomeric carbon centers, S-and R-, respectively. We note that Ruta et al used column chromatography of racemates and reported that L-histidine binds an RNA aptamer 1,000 times more tightly than does D-histidine 860-fold affinity difference between L-and D-histidine binding to RNA in a similar study (22).…”

Section: Resultssupporting

confidence: 51%

Deoxypolypeptides bind and cleave RNA

Cheng

Mahendran

Gonzalez

et al. 2014

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

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We have prepared L-and D-deoxypolypeptides (DOPPs) by selective reduction of appropriately protected polyhistidines with borane, reducing the carbonyl groups to methylenes. The result is a chiral polyamine, not amide, with a mainly protonated backbone and chirally mounted imidazolylmethylene side chains that are mostly unprotonated at neutrality because of the nearby polycationic backbone. We found that, in contrast with the D-octahistidine DOPP, the L-octahistidine DOPP is able to cooperatively bind to a D-polyuridylic acid RNA; this is consistent with results of previous studies showing that, relative to D-histidine, L-histidine is able to more strongly bind to RNA. The L-DOPP was also a better catalyst for cleaving the RNA than the D-DOPP, consistent with evidence that the L-DOPP uses its imidazole groups for catalysis, in addition to the backbone cations, but the D-DOPP does not use the imidazoles. The L-DOPP bifunctional process probably forms a phosphorane intermediate. This is a mechanism we have proposed for models of ribonuclease cleavage and for the ribonuclease A enzyme itself, based on our studies of the cleavage and isomerization of UpU catalyzed by imidazole buffers as well as other relevant studies. This mechanism contrasts with earlier, generally accepted ribonuclease cleavage mechanisms where the proton donor coordinates with the oxygen of the leaving group as the 2-hydroxyl of ribose attacks the unprotonated phosphate. T he enzyme ribonuclease A (RNase A) hydrolyzes RNA with bifunctional catalysis, using His-12 as a base and protonated His-119 as an acid to form the first products, a 2,3-cyclic phosphate of one ribose and the free next ribose with a new terminal 5′-hydroxyl group (1, 2). Lys-41 is also involved in stabilizing intermediate anions (3). In a second step the cyclic phosphate is hydrolyzed using the now-protonated His-12 and now-deprotonated His-119 in essentially a reverse of the cyclization step, with water replacing the second ribose unit (4). In the classical mechanism of this process it had been generally accepted, including in textbooks, that the protonated His-119 donates its proton to the leaving group whereas the 2′-hydroxyl group attacks the phosphate (1, 2) [isotope studies show that two protons are "in flight" during the hydrolysis step, essentially the reverse of the cyclization, both moving at the same time (5)]. We also showed the two-proton-in-flight process in a model system (6).However, our extensive studies on the cleavage of RNA with imidazole-imidazolium catalysts and on catalysis by RNase A itself indicated that a different mechanism is used ( Fig. 1) (7, 8). The proton donor BH + hydrogen binds to a phosphate oxyanion and donates the proton to the phosphate as the ribose 2′-hydroxyl adds while losing a proton to base :B. This process results in an intermediate phosphorane species. This then expels the 5′-hydroxyl group of the second nucleotide to cleave the P-O bond in a second step. We proposed this two-step phosphorane process to be the preferred path for th...

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Section: Resultssupporting

confidence: 51%

Deoxypolypeptides bind and cleave RNA

Cheng

Mahendran

Gonzalez

et al. 2014

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

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“…Interestingly, compound 39 f exhibited significant sequence selectivity for the D-arm of tRNA Lys 3 , and lost the capacity to bind to the T-arm of tRNA Lys 3 , even at a high ligand-tRNA ratio (see Supporting Information). Because this study was conducted with racemic compounds, the stereospecificity of the binding was evaluated for compound 39 f. [18] Each enantiomer was prepared and individually studied. Both enantiomers interacted with the same region of the tRNA, with a similar strength.…”

Section: Resultsmentioning

confidence: 99%

Design of tRNA^Lys₃ Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy

Chung

Tisné

Lecourt

et al. 2009

Chemistry A European J

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A fragment-based approach for the synthesis of ligands of tRNA(Lys) (3), the HIV reverse-transcription primer, is described. The use of NMR spectroscopy has proved to be very useful in this approach, not only to detect low-affinity complexes between small compounds and RNA, but also to provide information on their binding mode and on the way they can be connected. This NMR-spectroscopy-guided analysis enabled us to design micromolar ligands after the optimisation and connection of millimolar fragments with an appropriate linker. The influence of the linker region on the binding affinity and selectivity outlines the importance of having a flexible assemblage strategy with a variety of linkers in such an approach.

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“…a primordial t RNA as advanced by Yarus (1989) or serving as a template for building the first peptides, these ones catalyzing later the XNA synthesis in a positive evolutionary loop. The argument ''extented anti-codon'' claims that the t RNA-AA bond can involve bases of the anti-codon loop other than strictly those of the anti-codon (Majerfeld et al 2005;Knight and Landweber 1998), this mechanism being similar to an aptameric AL-AA link (especially with amino-acids like arginine, lysine or tyrosine).…”

Section: Al and Present Rna Relicsmentioning

confidence: 99%

Evolution and RNA Relics. A Systems Biology View

Demongeot¹,

Glade²,

Moreira³

2008

Acta Biotheor

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The genetic code has evolved from its initial non-degenerate wobble version until reaching its present state of degeneracy. By using the stereochemical hypothesis, we revisit the problem of codon assignations to the synonymy classes of amino-acids. We obtain these classes with a simple classifier based on physico-chemical properties of nucleic bases, like hydrophobicity and molecular weight. Then we propose simple RNA (or more generally XNA, with X for D, P or R) ring structures that present, overlap included, one and only one codon by synonymy class as solutions of a combinatory variational problem. We compare these solutions to sequences of present RNAs considered as relics, with a high interspecific invariance, like invariant parts of (t)RNAs and micro-RNAs. We conclude by emphasizing some optimal properties of the genetic code.

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RNA Affinity for Molecular L-Histidine; Genetic Code Origins

Cited by 60 publications

References 23 publications

Deoxypolypeptides bind and cleave RNA

Deoxypolypeptides bind and cleave RNA

Design of tRNA^Lys₃ Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy

Evolution and RNA Relics. A Systems Biology View

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RNA Affinity for Molecular L-Histidine; Genetic Code Origins

Cited by 60 publications

References 23 publications

Deoxypolypeptides bind and cleave RNA

Deoxypolypeptides bind and cleave RNA

Design of tRNALys3 Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy

Evolution and RNA Relics. A Systems Biology View

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Design of tRNA^Lys₃ Ligands: Fragment Evolution and Linker Selection Guided by NMR Spectroscopy