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Conformational Preferences of Modified Nucleoside 5-Taurinomethyluridine, τm5U Occur at ‘wobble’ 34th Position in the Anticodon Loop of tRNA

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Abstract

Conformational preferences of hypermodified nucleoside 5-taurinomethyluridine 5′-monophoshate ‘p-τm5U’ (–CH2–NH2 +–CH2–CH2–SO3 −) have been investigated using semi-empirical RM1 method. Automated geometry optimization using ab initio molecular orbital HF-SCF (6-31G**) and DFT (B3LYP/6-31G**) calculations have also been made to compare the salient features. The RM1 preferred most stable conformation of ‘p-τm5U’ has been stabilized by hydrogen bonding interactions between O(11a)…HN(8), O1P(34)…HN(8), and O1P(34)…HC(10). Another conformational study of 5-taurinomethyluridine side chain has also been performed in context of anticodon loop bases of E. coli tRNALeu. The atom O(11a) of τm5U(34) side chain interacts with adenosine (A35) as well as ribose–phosphate backbone which might provide structural stability to the anticodon loop. The glycosyl torsion angle of τm5U retains ‘anti’-conformation. The solvent accessible surface area calculations revealed the role of τm5U in tRNALeu anticodon loop. MD simulation results are found in agreement with RM1 preferred stable structure. The MEPs calculations of τm5U(34):G3 model show unique potential tunnels between the hydrogen bond donor and acceptor atoms as compared to τm5U(34):A3 model. Thus, these results could pave the way to understand the role of τm5U(34) to recognize UUG/UUA codons at atomic level in the mitochondrial disease, MELAS.

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Acknowledgments

KDS is gratefully acknowledged to University Grants Commission (UGC), New Delhi for financial support under the major research Project, vide UGC Letter No. F. 40-204/2011 (SR) dated June 29, 2011. ASK, BVK, and RSB are thankful to UGC for providing project fellowship.

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  1. Structural Bioinformatics Unit, Department of Biochemistry, Shivaji University, Kolhapur, 416004, Maharashtra, India

    Asmita S. Kamble, Bajarang V. Kumbhar, Susmit B. Sambhare, Rohit S. Bavi & Kailas D. Sonawane

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  1. Asmita S. Kamble
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Kamble, A.S., Kumbhar, B.V., Sambhare, S.B. et al. Conformational Preferences of Modified Nucleoside 5-Taurinomethyluridine, τm5U Occur at ‘wobble’ 34th Position in the Anticodon Loop of tRNA. Cell Biochem Biophys 71, 1589–1603 (2015). https://doi.org/10.1007/s12013-014-0382-x

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