Acharya, Parag ORCID: https://orcid.org/0000-0003-2521-9968, Nawrot, Barbara, Sprinzl, Mathias and Chattopadhyaya, Jyoti B. (1999) The strength of the 3′-gauche effect dictates the structure of 3′-O-anthraniloyladenosine and its 5′-phosphate, two analogues of the 3′-end of aminoacyl-tRNA. Journal of the Chemical Society. Perkin Transactions 2, 2 (7). pp. 1531-1536. ISSN 1472-779X (Print), 1364-5471 (Online) (doi:10.1039/a809350d)

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Abstract

Anthranilic acid charged yeast tRNAPhe or E. coli tRNAVal are able to form a stable complex with EF-Tu*GTP, hence the 2′- and 3′-O-anthraniloyladenosines and their 5′-phosphate counterparts have been conceived to be the smallest units that are capable of mimicking aminoacyl-tRNA. Since the 3′-O-anthraniloyladenosine also binds more efficiently to the EF-Tu*GTP complex compared to its 2′-isomer, we have herein delineated the stereoelectronic features that dictate the conformation of 3′-O-anthraniloyladenosine and its 5′-phosphate vis-a-vis their 2′-counterparts and we have also addressed how their structures and thermodynamic stabilizations are different from adenosine and 5′-AMP. It has been found that the electron-withdrawing anthraniloyl group exerts gauche effects of variable strengths depending upon whether it is at the 2′- or at 3′-position because of either the presence or absence of O2′–N9 gauche effect, [GE(O2′–C2′–C1′–N9)], thereby steering the pseudorotation of the constituent sugar moiety either to the North (N)-type (C3′-endo) or South (S)-type (C2′-endo) conformation. The 3′-O-anthraniloyladenosine 5′-phosphate has a relatively more stabilized S-type conformation ΔG ° = –4.6 kJ mol–1) than 3′-O-anthraniloyladenosine itself (ΔG ° = –3.9 kJ mol–1), whereas the ΔG ° for 2′-O-anthraniloyladenosine and its 5′-monophosphate are respectively –0.9 and –1.8 kJ mol–1, suggesting that the 3′-gauche effect of the 3′-O-anthraniloyl group is stronger than that of 2′-O-anthraniloyl in the drive of the sugar conformation. Since the EF-Tu can specifically recognize the aminoacylated-tRNA from the non-charged tRNA, we have assessed the free-energy (ΔG °) for this recognition switch to be the least ≈ –2.9 kJ mol–1 by comparison of ΔG ° of the N⇄pseudorotational equilibrium for 3′-O-anthraniloyladenosine 5′-phosphate and 5′-AMP. The 3′-O-anthraniloyladenosine and its 5′-phosphate are much more flexible than the isomeric 2′-counterparts as is evident from the temperature-dependent coupling constants analysis. The relative rate of the transacylation reaction of 2′(3′)-O-anthraniloyladenosine and its 5′-phosphate is cooperatively dictated by the two-state N⇄S pseudorotational equilibrium of the sugar, which in turn is controlled by a balance of the stereoelectronic 3′- and 2′-gauche effects as well as by the pseudoaxial preference of the 3′-O- or 2′-O-anthraniloyl group. The reason for the larger stabilization of the 2′-endo conformer for 3′-O-anthraniloyladenosine and its 5′-phosphate lies in the fact that the C3′–O3′ bond takes up an optimal gauche orientation with respect to the C4′–O4′ bond dictating the pseudoaxial orientation of the 3′-anthraniloyl residue, which can be achieved only in the S-type sugar conformation with adenin-9-yl and the 2′-OH groups in the pseudoequatorial geometry, compared to the preferred C3′-endo sugar with a pseudoaxial aglycone and 2′-OH found in the 3′-terminal adenosine moiety in the helical 3′-CCA end of uncharged tRNA.

Item Type:	Article
Uncontrolled Keywords:	t-RNA, NMR conformation, gauche effect
Subjects:	Q Science > Q Science (General)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > Natural Resources Institute Faculty of Engineering & Science > Natural Resources Institute > Food & Markets Department
Last Modified:	08 Jul 2020 12:09
URI:	http://gala.gre.ac.uk/id/eprint/28734

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