Iso-energetic multiple conformations of hypermodified nucleic acid base wybutine (yW) which occur at 37th position in anticodon loop of tRNAPhe

Kumbhar, Navanath; Sonawane, Kailas D.

doi:10.1016/j.jmgm.2011.03.005

Cited by 17 publications

(38 citation statements)

References 51 publications

(100 reference statements)

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“…Such sort of H bonding bridges was also noted in the case of 'wobble' 34th position protonated variant hypermodified nucleoside pQH? during MD simulation [34] as well as in case of other biomolecules [42,44]. These effects are also in close harmony with LA-MB-FTMW spectroscopy studied stable conformer I of isolated 2-amino-ethanesulfonic acid, taurine [68].…”

Section: Methodssupporting

confidence: 75%

“…2) was used as a starting structure for the 5-ns molecular dynamics simulation study. MD simulation studies within 5-ns time period have been found valuable to appreciate the conformational preferences of modified nucleosides such as Que [34], ac 4 C [56], yW [42], OHyW [44], and m 2 G and m 2 2 G [70]. The results of analyzed average (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…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].…”

Section: Methodsmentioning

confidence: 99%

“…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].…”

Section: Methodsmentioning

confidence: 99%

“…All calculations were performed on HP xw8600 workstation and HP ProLiant DL180G6 Rack Server. Molecular dynamics simulation protocol analogous to earlier study has been applied [42,44]. Kollman all-atom force field [64] in the company of Gasteiger-Marsili charges in addition to TIP3P model water was used in this study.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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The myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial encephalomyopathic disease caused due to the lack of hypermodified nucleoside 5-taurinomethyl-2-thiouridine at 'wobble' 34th position in the anticodon loop of human mitochondrial tRNA Lys . Understanding the structural significance of sm 5 s 2 U might be helpful to get more information about the MERRF disease in detail at the atomic level. Hence, conformational preferences of hypermodified nucleoside 5-taurinomethyl-2-thiouridine 5 0 -monophosphate, 'p-sm 5 s 2 U,' have been studied using semiempirical quantum chemical RM1 method. Full geometry optimization using ab initio molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) methods has also been used to compare the salient features. The RM1 preferred most stable conformation of 'p-sm 5 s 2 U' has been stabilized by hydrogen bonding interactions between O(11a)…HN (8), O1P (34) … HN(8), O1P (34) …HC(10), O4 0 (34) …HC(6), S(2)…HC1 0 (34), O5 0 (34) …HC(6), and O(4)…HC (7). Another conformational study of 5-taurinomethyl-2-thiouridine side chain in the presence of anticodon loop bases of human mitochondrial tRNA Lys showed similar conformation as found in RM1 preferred most stable conformation of 'p-sm 5 s 2 U.' The glycosyl torsion angle of sm 5 s 2 U retains 'anti' conformation. Similarly, MD simulation results are also found in accordance with RM1 preferred stable structure. The solvent-accessible surface area calculations revealed surface accessibility of sm 5 s 2 U in human mt tRNA Lys anticodon loop. The MEPs calculations of codon-anticodon models of sm 5 s 2 U (34) :G 3 and sm 5 s 2 U (34) :A 3 showed unique potential tunnels between the hydrogen bond donor and acceptor atoms. These results might be useful to understand the exact role of sm 5 s 2 U (34) to recognize AAG/ AAA codons and to design new strategies to prevent mitochondrial disease, MERRF.

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Section: Methodssupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

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

et al. 2015

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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

Bavi

Kamble

Kumbhar

et al. 2011

Cell Biochem Biophys

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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.

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Conformational Preferences of Modified Nucleoside N(4)-Acetylcytidine, ac4C Occur at “Wobble” 34th Position in the Anticodon Loop of tRNA

Kumbhar

Kamble

Sonawane

2013

Cell Biochem Biophys

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Conformational preferences of modified nucleoside, N(4)-acetylcytidine, ac(4)C have been investigated using quantum chemical semi-empirical RM1 method. Automated geometry optimization using PM3 method along with ab initio methods HF SCF (6-31G**), and density functional theory (DFT; B3LYP/6-31G**) have also been made to compare the salient features. The most stable conformation of N(4)-acetyl group of ac(4)C prefers "proximal" orientation. This conformation is stabilized by intramolecular hydrogen bonding between O(7)···HC(5), O(2)···HC2', and O4'···HC(6). The "proximal" conformation of N(4)-acetyl group has also been observed in another conformational study of anticodon loop of E. coli elongator tRNA(Met). The solvent accessible surface area (SASA) calculations revealed the role of ac(4)C in anticodon loop. The explicit molecular dynamics simulation study also shows the "proximal" orientation of N(4)-acetyl group. The predicted "proximal" conformation would allow ac(4)C to interact with third base of codon AUG/AUA whereas the 'distal' orientation of N(4)-acetyl cytidine side-chain prevents such interactions. Single point energy calculation studies of various models of anticodon-codon bases revealed that the models ac(4)C(34)(Proximal):G3, and ac(4)C(34)(Proximal):A3 are energetically more stable as compared to models ac(4)C(34)(Distal):G3, and ac(4)C(34)(Distal):A3, respectively. MEPs calculations showed the unique potential tunnels between the hydrogen bond donor-acceptor atoms of ac(4)C(34)(Proximal):G3/A3 base pairs suggesting role of ac(4)C in recognition of third letter of codons AUG/AUA. The "distal" conformation of ac(4)C might prevent misreading of AUA codon. Hence, this study could be useful to understand the role of ac(4)C in the tertiary structure folding of tRNA as well as in the proper recognition of codons during protein biosynthesis process.

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Iso-energetic multiple conformations of hypermodified nucleic acid base wybutine (yW) which occur at 37th position in anticodon loop of tRNAPhe

Cited by 17 publications

References 51 publications

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

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

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

Conformational Preferences of Modified Nucleoside N(4)-Acetylcytidine, ac4C Occur at “Wobble” 34th Position in the Anticodon Loop of tRNA

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