Structural significance of modified nucleosides k2C and t6A present in the anticodon loop of tRNAIle

Abstract

The structural significance of the hypermodified nucleosides lysidine (k 2 C) and N 6 -(N-threonylcarbonyl) adenosine (t 6 A) present in the anticodon loop of E. coli tRNA Ile has not been studied in detail theoretically at the atomic level. Hence, in the present paper, we investigated the conformational preferences of modified nucleosides k 2 C and t 6 A in the anticodon loop of tRNA Ile using various quantum chemical methods. Multiple molecular dynamics simulation studies of the anticodon stem loop (ASL) of tRNA Ile have also been made to see the solvation effect. The lysine moiety of lysidine orients back and forms a hydrogen bond with the 2 0 -hydroxyl group of the 34th ribose sugar whereas the t 6 A (37) side chain prefers a 'distal' conformation. This kind of conformation would be useful for recognition of the codons AUA instead of AUG. The t 6 A side chain prohibits canonical base pairing and maintains an anticodon open loop structure. The preferred conformations of k 2 C (34) and t 6 A (37) are stabilized by various intra as well as inter residual interactions within the anticodon loop which could be useful for maintaining a proper anticodon loop structure for smooth and in phase codon-anticodon interactions during the biosynthesis of proteins.

Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

“…8a) have been carried out using semiempirical RM1 method to get the overall idea about the conformational space of sm 5 s 2 U similar to earlier studies [32,56,80]. The initial torsion angle values for sm 5 s 2 U (34) have been utilized from the side chain of RM1 preferred most stable conformation of 'p-sm 5 s 2 U' as shown in Fig.…”

Celebrating wobble decoding: Half a century and still much is new

“…t 6 A 37 also facilitates ribosomal codon binding and maintains the translational frame. 26,126 Other modifications at position 37, particularly in tRNAs responding to codons beginning with U, UNN, such as wyosine, contribute similarly to base stacking, maintaining the open loop structure and by doing so maintain the translational reading frame. 26,126 The fact that the ASL can be stabilized by various purine 37 modifications implies convergent evolutionary pathways that relate not only to the identity of the codon, but also to that of the nucleoside at position 34 and perhaps additionally either 32 or 38/39.…”

“…126 Agmatidine forms a similar tautomer as lysidine. 122,126 The hydrogen bonding capability of modified nucleosides commonly found at the wobble position of tRNA Ile illustrates how small changes in the chemistry of a single nucleoside can have broad and highly specific effects, in this case altering codon recognition and specificity while simultaneously preserving aaRS recognition. 121 …”

RM1 Semiempirical Model: Chemistry, Pharmaceutical Research, Molecular Biology and Materials Science

“…Indeed, many articles report its use in these contexts. 34,[225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243][244] For example, Aldulaijan and Platts 244 studied the peptide binding to the histocompatibility II receptors. Statistical results indicated a correlation between the half maximal inhibitory concentration (IC 50 ) and RM1-D interaction energy.…”