Similar Conformations of Hairpins with TTT and TTTT Sequences NMR and Molecular Modeling Evidence for T · T base pairs in the TTTT hairpin

Abstract

"P signals of the two hairpins have been nearly completely assigned by means of two-dimensional NMR spectroscopy in D,O (NOESY (two-dimensional nuclear Overhauser effect and exchange spectroscopy) at mixing times of 5, 50, 100, 300 and 500 ms, double-quantum-filtered correlation spectroscopy (DQF-COSY) and 'H-"P reverse chemical shift correlation (RCSC), and one-dime,nsional NOE spectra in 90% H,O. Conformational analysis using distance geometry (DG), molecular mechanics (MM) and molecular dynamics (MD) gave model conformations, which were evaluated by comparison of experimental and simulated 2D NOESY spectra. For the T, sequence in T4, both NMR data and modeling indicated a T(a) . (5) of T3] has a gauche', gauche' <,a conformation with a trans y angle for the second residue in both. These or similar features appear to be present in most of the few other hairpins studied previously by conformational methods. Thus, we believe that the conformations of the loops in T, and T, hairpins have greater similarities than previously recognized.

The Transition from a Neutral-pH Double Helix to a Low-pH Triple Helix Induces a Conformational Switch in the CCCG Tetraloop Closing a Watson-Crick Stem

“…For three-membered loops similar patterns can be distinguished, as has, e.g. very recently been illustrated by Kuklenyik et al (1996).…”

The Hairpin Structure of a Topoisomerase II Site DNA Strand Analyzed by Combined NMR and Energy Minimization Methods

“…Table 6 gathers the torsion angle values for the so-called turning phosphate, i.e. the position where a change of direction occurs in the phosphate backbone in a variety of reported DNA hairpin loops (Mooren et al, 1994;Boulard et al, 1991;Kuklenyik et al, 1996;Blommers et al, 1991;Hirao et al, 1994). In four of the represented structures (Mooren et al, 1994;Boulard et al, 1991;Kuklenyik et al, 1996;Blommers et al, 1991) the turning phosphate displays a combination z(+)a(+)b(t)g(t) similar to that of T10pC11 in our structure.…”

Structural similarities and differences between H1- and H2-family DNA minihairpin loops: NMR studies of octameric minihairpins

“…Other candidates that contain conformational mixtures for both loop foldings are the 5Ј-d(CGCA-TC-TGCG)-3Ј hairpin, containing an -ATCT-loop, 60 and sequences containing a -TTTT-loop. 9,16,17,61 In both cases, a relative fast exchange occurs between structures having a H2-family and a H1-family loop folding.…”

“…In addition, a reduction of the space required to fit in the closing base pair is another way to remove steric strain in the loop. This is the reason why noncanonical base pairs like a G-A, 11 a wobble T-T, 9,16,17 a Hoogsteen T-A, 18 and a G(syn)-C ϩ10 closing base pair can effectively stabilize tight hairpin loops with the aid of their unusual base pairing schemes consisting of a reduced intrastrand C1Ј-C1Ј distance compared to that in canonical Watson-Crick base pairs. In our terminology a minihairpin is defined as a two-residue loop, in which the bases closing the loop lie in an approximately planar geometry and are connected by at least one hydrogen bond.…”

“…Detailed nmr structures of various H2-family hairpins, having a pyrimidine in the leading position, are now available, 6,9,10,18 from which it is concluded that these minihairpin loops within experimental error share a common basic folding principle, c.q. the position of the first loop residue in the minor groove (-a CTAG-, -CTTG-, -TTTA-, -CCCG-, and -TTTTloop sequences, respectively).…”