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

Abstract

Conformational preferences of hypermodified nucleoside 5-taurinomethyluridine 5'-monophoshate 'p-τm(5)U' (-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-τm(5)U' 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 tRNA(Leu). The atom O(11a) of τm(5)U(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 τm(5)U retains 'anti'-conformation. The solvent accessible surface area calculations revealed the role of τm(5)U in tRNA(Leu) anticodon loop. MD simulation results are found in agreement with RM1 preferred stable structure. The MEPs calculations of τm(5)U(34):G3 model show unique potential tunnels between the hydrogen bond donor and acceptor atoms as compared to τm(5)U(34):A3 model. Thus, these results could pave the way to understand the role of τm(5)U(34) to recognize UUG/UUA codons at atomic level in the mitochondrial disease, MELAS.

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

“…The glycosyl torsion angle 'v' when allowed to change freely over the entire range 0-360°retained initial value (v = 28.7°), i.e., 'anti' conformation similar to crystal structure of tRNA Leu containing sm 5 U at 34th position [33], p-sm 5 U [32], lysidine (k 2 C) [55], Queuosine [34], and ac 4 C [56]. The 'anti' (v = 28.7°) conformation of glycosyl torsion angle would be useful to allow wobble 34th position sm 5 s 2 U atoms O(4), HN(3), and S(2) to interact with the last base of codons AAG/AAA all through protein biosynthesis process.…”

“…6) with the help of Spartan ver 6.0.1 software [35] as calculated for the base pair model of sm 5 U 34 :G 3 [32], ac 4 C(Proximal/Distal) 34 :G 3 /A 3 [56]. The color scale range of sm 5 s 2 U 34 :G 3 base pair model is in between -6.5 Min to 2.2 Max V. The MEPs show three distinct potential tunnels between hydrogen bond donor and acceptor atoms of sm 5 s 2 U 34 :G 3 model (Fig.…”

“…As we know that sm 5 s 2 U was derived from sm 5 U modification, so we utilized side chain torsion angle values as per the sm 5 U (34) at 34th position within crystal structure of tRNA Leu [33] and also verified by utilizing side chain torsion angle values of most stable conformation of 'psm 5 U' [32]. The phosphate backbone torsion angles are notable by subscript 'b' similar to Que [34] and sm 5 U [32].…”

“…The phosphate backbone torsion angles are notable by subscript 'b' similar to Que [34] and sm 5 U [32].…”

“…It has been explained that sm 5 U 34 :A 3 base pair comprises conventional geometry, while the sm 5 U 34 :G 3 base pair comprises non-conventional geometry with codon at wobble 34th position within tRNA Leu [32,33]. Therefore, it is of interest to discover the structural role of sm 5 s 2 U in respect of cognate G and A ending codons during protein biosynthesis process in mitochondrial tRNAs.…”