B and Z Forms of a Modified d(C-G) Sequence in Solution

Orbons, Leonard P. M.; Marel, Gijs A. van der; Boom, J. H. Van; Altona, C.

doi:10.1007/978-1-4615-8521-3_13

Cited by 22 publications

(36 citation statements)

References 13 publications

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“…The experimental procedures and the assignment of the 'H-NMR spectra of both DNA fragments is described in the preceding paper [24].…”

Section: Methodsmentioning

confidence: 99%

“…It should be noted that the low-salt form in aqueous solution is designated as B DNA and the form which becomes increasingly predominant when increasing amounts of salt and/or methanol are added to the solution is designated Z DNA, see companion paper [24].…”

Section: Fig 2 Conformational Notationmentioning

confidence: 99%

“…Mainly this is caused by the differences in the geometry of the R-Y and the Y-R steps. In the former steps the interresidue NOEs show close similarity to those of the A and B helices [that is Hd(n)/H-l'(n -l), H-2'(n -1) and H-2(n -1) NOEs], whereas the R-Y steps exhibit a completely different NOE pattern, H-8(n), H-l'(n)/H4'(n -l), H-S(n -1) and H-5"(n -1) NOEs [24]. Besides the observation of such a characteristic asymmetric NOE pattern, a second feature of Z DNA, as monitored by NOESY, is given by the syn position of the guanine bases in the Z form [19,201, which implies a very short intraresidue proton-proton distance between the H-8 and the H-1' (0.24 nm).…”

Section: Noesmentioning

confidence: 99%

“…For example, Fig.4 shows a stacked plot of a part of the NOESY spectrum which traces the NOEs between the base and H-1' protons. The two crosssections in Fig.4 Further details of the NOE pattern of the Z and B species in the 2HzO/C2H302H (70/30) mixture (5 mM MgCI2) are described in a companion paper [24]. Suffice it to say that the DNA form which becomes increasingly predominant when increasing amounts of salt and/or methanol are added to the solution, exhibits Z-type characteristics as derived from COSY and NOESY.…”

Section: Noesmentioning

confidence: 99%

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Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution

Orbons

Altona

1986

European Journal of Biochemistry

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The B and the Z forms of the DNA hexamers d(m5C-G)3 and d(b~-%-G)~ were investigated by means of NMR spectroscopy. It is demonstrated that the low-salt form of d(m5C-G)3 is a B DNA structure. The form, which becomes increasingly predominant when increasing amounts of MgC12 and/or methanol are added to the solution, has Z DNA characteristics. It is shown that the major geometrical features of the Z form of d(mSC-G)3 in the crystal structure are maintained in solution, with the dC residues S sugar conformation, y ' and the base in the anti orientation and the dG residues N (except the 3'-terminal residue), yf and syn. Neither the Z form of the methylated nor that of the brominated compound resembles the Z form, in which the deoxy guanosine sugar rings adopt a Cl'-exo conformation. Substitution of m5C by br5C causes no perceptible conformational changes in either the B or in the Z forms.The polymorphism exhibited by the DNA double helix [I, 21 has fascinated investigators from many fields of research for a long time. It is becoming clear that the character of the bases (purine R or pyrimidine Y) and their sequence determine the conformational possibilities of a given DNA species. For example, the peculiar inversion of the CD spectrum of poly d(G,C) . poly d(G,C) upon addition of salt [3] and/or alcohols [4,5] appeared limited to polymer duplex species that contain alternating dC-dG sequences and few others (dA-dC, dT-dG). This inversion was later shown to be a consequence of the conversion of the right-handed B DNA form into the lefthanded Z DNA species 16, 71. Detailed NMR and CD studies have revealed that Z DNA can be stabilized chemically in several ways. For instance, methylation [8,9] or bromination [lo-121 at the C-5 position of cytosine, or bromination at the C-8 position of guanine [13, 141 shifts the equilibrium between the B and Z forms towards the latter DNA species.Up till now information concerning the detailed geometry of Z DNA has come almost exclusively from X-ray crystallography 1151. In contrast to the classical B form, Z DNA has only a minor groove, which resembles the minor groove of B DNA. The major groove of B DNA constitutes an outer surface of Z DNA and exposes the cytosine C-5 and guanine N-7 and C-8 atoms. The major geometrical characteristics of Z DNA in the crystal can be summarized as follows: (a) the pyrimidines ( Y ) adopt a standard conformation with S-type sugar pucker, base anti (Fig. l ) and g + orientation about torsion angle y (Fig. 2); (b) the purines (R) prefer This paper is number 46 in a series Nucleic Acid Constituents from this laboratory; for part 45 see the preceding paper in this journal.Abbreviations. Me,NCI, tetramethylammonium chloride; NOE, nuclear Overhauser effect; NOESY, two-dimensional nuclear Overhauser spectroscopy; COSY, correlated spectroscopy. N-type sugars, base syn (Fig. I) and a g' rotamer about y ; (c) the phosphodiester bonds adopt the (+, a+ rotamer combination for the Y-R step and usually l -, a' for the R-Y step. It should be mentioned here that spe...

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“…The experimental procedures and the assignment of the 'H-NMR spectra of both DNA fragments is described in the preceding paper [24].…”

Section: Methodsmentioning

confidence: 99%

Section: Fig 2 Conformational Notationmentioning

confidence: 99%

Section: Noesmentioning

confidence: 99%

Section: Noesmentioning

confidence: 99%

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Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution

Orbons

Altona

1986

European Journal of Biochemistry

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“…Several structural studies by single-crystal x-ray diffraction and NMR methods have shown that G-A mismatches are conformationally variable. Base pairs of types A and B but not C and D have been observed (7,(15)(16)(17)(18)(19)(20).In studies of the interaction of antisense oligonucleotides with 11-base analogs of ras p21 mRNA (21), we discovered a sequence, termed 2C, 5'-d(ATGAGCGAATA), that formed an unusually stable duplex (22). Eight of 11 bases in sequence 2C are purines and, from base-pairing possibilities, an unusual duplex with four G-A mismatch base pairs was proposed for this sequence (Fig.…”

mentioning

confidence: 99%

NMR and molecular modeling evidence for a G.A mismatch base pair in a purine-rich DNA duplex.

Liu

Zon

Wilson

1991

Proc. Natl. Acad. Sci. U.S.A.

151

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ABSTRACT1H NMR experiments indicate that the oligomer 5'-d(ATGAGCGAATA) forms an unusual 10-base-pair duplex with 4 G-A base pairs (underlined) and a 3' unpaired adenosine. NMR results indicate that guanosine imino protons of the G-A mismatches are not hydrogen bonded but are stacked in the helix. A G -* I substitution in either G-A base pair causes a dramatic decrease in duplex stability and indicates that hydrogen bonding of the guanosine amino group is critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional correlated spectroscopy (COSY) results indicate that the overall duplex conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY spectra between a mismatched AH2 and an AHl' ofthe other mismatched base pair and between a mismatched GH8 and GNH1 of the other mismatch establish a purine-purine stacking pattern, adenosine over adenosine and guanosine over guanosine, which strongly stabilizes the duplex. A computer graphics molecular model of the unusual duplex was constructed with G-A base pairs containing A-NH2 to GN3 and G-NH2 to AN7 hydrogen bonds and B-form base pairs on both sides of the G'A pairs [5'-d(ATGAGC)J. The energy-minimized duplex satisfies all experimental constraints from NOESY and COSY results. A hydrogen bond from G-NH2 of the mismatch to a phosphate oxygen is predicted.Mismatches in DNA can arise, for example, in specific structures such as telomeres (1, 2), during replication, and in genetic recombination. If not corrected, the mismatches may lead to point mutations in subsequent replication (3-7). G-A mismatches are of particular interest because they are a common structural element in RNA folding (8)(9)(10)(11). Early studies have shown that a single G&A mismatch could be readily incorporated into DNA helices and the G-A mismatch was resistant to single-strand nucleases (12, 13). In neutral aqueous buffer with the normal base tautomers, there are four types of G&A mismatch base pairs (14), and these can be grouped by imino (Fig. 1, structures A and B) or amino hydrogen bond (Fig. 1, structures C and D) pairs with respect to guanosine. Several structural studies by single-crystal x-ray diffraction and NMR methods have shown that G-A mismatches are conformationally variable. Base pairs of types A and B but not C and D have been observed (7,(15)(16)(17)(18)(19)(20).In studies of the interaction of antisense oligonucleotides with 11-base analogs of ras p21 mRNA (21), we discovered a sequence, termed 2C, 5'-d(ATGAGCGAATA), that formed an unusually stable duplex (22). Eight of 11 bases in sequence 2C are purines and, from base-pairing possibilities, an unusual duplex with four G-A mismatch base pairs was proposed for this sequence (Fig. 2a) (22). We have undertaken NMR studies to define this unusual duplex in more detail and report here the observations of G-A mismatches oftype D and unusual purine purine base stacking in a B-form duplex.MATERIALS AND METHODS Oligonucleotides were synthesized as described (22). NMR experiments were performed on a Varian...

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

et al. 1998

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TheDNA sequences 5′‐d(CGC‐AC‐GCG)‐3′ (HPAC), 5′‐d(CGC‐AA‐GCG)‐3′ (HPAA), 5′‐d(CGC‐TC‐GCG)‐3′ (HPTC), and 5′‐d(CGC‐CT‐GCG)‐3′ (HPCT), were studied by means of nmr spectroscopy. At low DNA concentration and no added salt all four molecules adopt a minihairpin structure, containing three Watson–Crick base pairs and a two‐residue loop. The structure of the HPAC hairpin is based on quantitative distance restraints, derived by a full relaxation matrix approach (iterative relaxation matrix approach), together with torsion angles obtained from coupling constant analysis. The loop folding is of the H1‐family type, characterized by continuous 3′‐5′ stacking of the loop bases on the duplex stem. The structure of the HPAA hairpin is similar to that of HPAC, but is more flexible and has a lower thermodynamic stability (Tm 326 K vs 320 K). According to “weakly” distance‐constrained simulations in water on the HPAC minihairpin, the typical H1‐family loop folding remains intact during the simulation. However, residue‐based R factors of simulated nuclear Overhauser effect spectroscopy spectra, free molecular dynamics simulations in vacuo, and unusual chemical shift profiles indicate partial destacking of the loop bases at temperatures below the overall melting midpoint. The dynamic nature of the loop bases gives insight into the geometrical tolerances of stacking between bases in H1‐family minihairpin loops. The HPTC and HPCT minihairpins, both containing a pyrimidine base at the first position in the loop, adopt a H2‐family type folding, in which the first loop base is loosely bound in the minor groove and the second loop base is stacked upon the helix stem. The thermal stability for these two hairpins corresponds to 327–329 K, but depends on local base sequence. Preference for the type of folding depends on a single substitution from a pyrimidine (H2 family) to a purine (H1 family) at the first position of the miniloop and is explained by differences in base stacking energies, steric size, and the number of possible candidates for hydrogen bonds in the minor groove. In view of newly collected data, previous models of the H1‐family and H2‐family hairpins had to be revised and are now compatible with the reported HPTC and HPAC structures. The structural difference between the refined structure of HPAC and HPTC show that a conversion between H1‐family and H2‐family hairpins is geometrically possible by a simple pivot point rotation of 270° along two torsion angles, thereby swiveling the first loop base from a stacked position in a H1‐family folding toward a position in the minor groove in a H2‐family folding. The second loop residue subsequently shifts to the position of the first base in a concerted fashion. © 1998 John Wiley & Sons, Inc. Biopoly 46: 375–393, 1998

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B and Z Forms of a Modified d(C-G) Sequence in Solution

Cited by 22 publications

References 13 publications

Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution

Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution

NMR and molecular modeling evidence for a G.A mismatch base pair in a purine-rich DNA duplex.

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

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B and Z Forms of a Modified d(C-G) Sequence in Solution

Cited by 22 publications

References 13 publications

Conformational analysis of the B and Z forms of the d(m5C‐G)3 and d(br5C‐G)3 hexamers in solution

Conformational analysis of the B and Z forms of the d(m5C‐G)3 and d(br5C‐G)3 hexamers in solution

NMR and molecular modeling evidence for a G.A mismatch base pair in a purine-rich DNA duplex.

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

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Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution

Conformational analysis of the B and Z forms of the d(m⁵C‐G)₃ and d(br⁵C‐G)₃ hexamers in solution