Conformational Preferences of Modified Nucleoside N2-methylguanosine (m2G) and Its Derivative N2, N2-dimethylguanosine (m 2 2 G) Occur at 26th Position (Hinge Region) in tRNA

Abstract

Conformational preferences of the modified nucleosides N(2)-methylguanosine (m(2)G) and N(2), N(2)-dimethylguanosine (m(2)(2)G) have been studied theoretically by using quantum chemical perturbative configuration interaction with localized orbitals (PCILO) method. Automated complete geometry optimization using semiempirical quantum chemical RM1, along with ab initio molecular orbital Hartree-Fock (HF-SCF), and density functional theory (DFT) calculations has also been made to compare the salient features. Single-point energy calculation studies have been made on various models of m(2)G26:C/A/U44 and m(2)(2)G26:C/A/U44. The glycosyl torsion angle prefers "syn" (χ = 286°) conformation for m(2)G and m(2)(2)G molecules. These conformations are stabilized by N(3)-HC2' and N(3)-HC3' by replacing weak interaction between O5'-HC(8). The N(2)-methyl substituent of (m(2)G26) prefers "proximal" or s-trans conformation. It may also prefer "distal" or s-cis conformation that allows base pairing with A/U44 instead of C at the hinge region. Thus, N(2)-methyl group of m(2)G may have energetically two stable s-trans m(2)G:C/A/U or s-cis m(2)G:A/U rotamers. This could be because of free rotations around C-N bond. Similarly, N(2), N(2)-dimethyl substituent of (m(2)(2)G) prefers "distal" conformation that may allow base pairing with A/U instead of C at 44th position. Such orientations of m(2)G and m(2)(2)G could play an important role in base-stacking interactions at the hinge region of tRNA during protein biosynthesis process.

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

“…Conformational preferences of hypermodified nucleoside 5-taurinomethyl-2-thiouridine 5 0 -monophosphate, 'p-sm 5 s 2 U', have been investigated in silico by using semiempirical Recife Model 1 (RM1) [36]. RM1 method has been useful to search conformational space of diverse organic and bioorganic molecules [37][38][39][40][41] and extensively used on account of its accurate and reasonable results [42][43][44][45]. The detailed process for conformational search in the multidimensional conformational space has already been described in our previous studies [42][43][44].…”

“…Conformational energy calculations have been performed to understand the structural significance of various hypermodified nucleosides, for example lysidine, k 2 C [55], N(4)-acetylcytidine, ac 4 C [56], queuosine [34] present at 'wobble' (34th) position and modifications present at '3'-adjacent' (37th) position together with their protonation effect such as wybutine (yW) and hydroxywybutine (OHyW) [42,44], t 6 Ade, g 6 Ade [57,58], i 6 Ade and ms 2 i 6 Ade [59], cis-io 6 Ade, trans-io 6 Ade, cis-ms 2 io 6 Ade and trans-ms 2 io 6 Ade [60], gc 6 Ade [61], tc 6 Ade [62] as well as m 2 G and m 2 2 G which occur at the tRNA hinge region of tRNA [43].…”

Structural significance of hypermodified nucleic acid base hydroxywybutine (OHyW) which occur at 37th position in the anticodon loop of yeast tRNAPhe

“…The PM3 method is implemented in commercially available PC Spartan Pro (version 6.1.1.0, Wavefunction Inc.) software [27]. Earlier conformational preferences of various modified nucleic acid bases and protonation induced conformational changes of these have been studied [28][29][30][31][32][33][34].…”

“…PCILO method has been found useful in conformational studies of bio-organic molecules [36,37], as well as for various hypermodified nucleosides [28,34]. The ribose-phosphate backbone has been adopted from yeast tRNA Phe crystal structure [26].…”

Statistical-Based Approach in Potential Diagnostic Application of Urinary Nucleosides in Urogenital Tract Cancer

“…In the available literature, conformational study showed that interaction between N2mG and A is possible and may exhibit a certain role in recognition of cytidine and uridine at the hinge region of tRNA. Moreover, appropriate orientation of N2mG might be influential in base-stacking during interactions at the hinge region of tRNA facilitating the process of protein biosynthesis [61]. What's more, since a consequence of G methylation is related to pairing between G and A [54], statistical interaction may possibly reflect this multiplicative effect.…”