Conformation of the circular dumbbell d〈pCGC-TT-GCG-TT〉: Structure determination and molecular dynamics

Ippel, Hans; Lanzotti, Virginia; Galeone, Aldo; Mayol, Luciano; Boogaart, Jacquelien E. van den; Pikkemaat, Jeroen A.; Altona, C.

doi:10.1007/bf00197639

Cited by 28 publications

(59 citation statements)

References 65 publications

(65 reference statements)

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“…6 A "weakly constrained" MD simulation of the HPAC hairpin in water (wMD) was performed at 300 K, with an arbitrarily choosen force constant K dc of 0.4 kJ/ mol ⅐ Å 2 on the distance constraints and E tc 0.4 kJ/mol on torsion angles. The molecule was immersed in a rectangular box of Monte Carlo TIP3P water molecules.…”

Section: Restrained Molecular Dynamics Simulationsmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Restrained Molecular Dynamics Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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“…This class of loops has been extensively studied by Altona and collaborators, all at neutral pH (Orbons et al, 1987;Ippel et al, 1992;Ippel, 1993). Common features are the Watson-Crick C·G pair, and the position of the Y base in the minor groove (type II).…”

Section: Structural Features Of the Cccg-loop At Neutral Phmentioning

confidence: 99%

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

Dongen¹,

Wijmenga

Marel

et al. 1996

Journal of Molecular Biology

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The CCCG-loop in a DNA fragment, which is capable of forming an Structure, Design, and intramolecular triple helix as well as a hairpin structure, was investigated Synthesis, Laboratory of by NMR and molecular modeling studies. We used molecular modeling to lay the foundations for understanding 2300 RA Leiden the observed conformational switch. A lower amount of strain, related to The Netherlands the short C1'-C1' of the base-pair, and protonation effects of the structure comprising the Hoogsteen base-pair turn out to outweigh the effects of a more stable base-pair, improved stacking and more favorable interactions in the minor groove of the structure comprising the Watson-Crick C·G base-pair. The models also provide an explanation for the general preference of loops meeting the consensus sequence -d(CYNG)-to fold into a type II conformation, i.e. with the base of second loop residue turned into the minor groove.

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“…In these cases, conformationally constrained oligonucleotides are more suitable models than the pure DNA fragments. 1 Cyclic oligonucleotides are a particular case of constrained oligonucleotides that have been used as models for studying DNA hairpins 2 and quadruplex structures, 3 and have been very useful in many thermodynamic studies. A more general approach to stabilize oligonucleotides is to connect the different strands that make up the structure with a cross-link.…”

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confidence: 99%

Solution structure and stability of a disulfide cross-linked nucleopeptide duplex

et al. 2003

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NMR methods are used to study the structure and stability of the duplex formed by the nucleopeptide [Ac-Cys-Gly-AlaHse(p 3A dGCATGC)-Ala-OH] 2 [S-S], in which the oligonucleotide is self-complementary and the cysteine residues of the two peptide chains form a disulfide bridge; thermal transitions and NMR-derived structural calculations are consistent with a 3-D structure in which the oligonucleotide forms a standard B-DNA helix without significant distortions; the peptide chains are relatively disordered in solution and lie in the minor groove of the DNA helix; this nucleopeptide duplex exhibits a high melting temperature, indicating that peptide-oligonucleotide conjugates containing cysteines are suitable molecules to establish cross-links between DNA strands and stabilize the duplex.Conformationally constrained oligonucleotides are interesting models for a variety of DNA structures, which include hairpins, cruciforms, triplexes, and so on. In many occasions, these noncanonical DNA structures are difficult to study in short oligonucleotide fragments because of their inherent flexibility. In these cases, conformationally constrained oligonucleotides are more suitable models than the pure DNA fragments. 1 Cyclic oligonucleotides are a particular case of constrained oligonucleotides that have been used as models for studying DNA hairpins 2 and quadruplex structures, 3 and have been very useful in many thermodynamic studies. A more general approach to stabilize oligonucleotides is to connect the different strands that make up the structure with a cross-link. Cross-linked oligonucleotides can be obtained in a variety of ways, but one of the most often used methods is through incorporation of thiol groups and formation of a disulfide bridge. Such an approach has been used to study different constrained DNA 4 and RNA structures. 5 Nucleopeptides are peptide-oligonucleotide conjugates with a covalent phosphodiester bond between the hydroxyl group of an aminoacid side chain and the 3A-or 5A-terminal hydroxyl group of an oligonucleotide chain (Fig. 1A). This kind of bond occurs in some covalently-linked protein-DNA complexes. In addition, the fact that the peptide chain is linked to the 3A-end of the oligonucleotide chain makes these molecules more resistant to exonucleases. 6 Peptide-oligonucleotide conjugates are also interesting because of their pharmaceutical relevance as antisense or antigene compounds. These and other potential applications of these conjugates have been reviewed recently. 7 The aim of this study is to explore the possibility of using peptides to establish a cross-link between opposing DNA strands. In this communication we report on the structure and thermodynamics of the duplex formed by the nucleopeptide [Ac-Cys-Gly-Ala-Hse(p 3A dGCATGC)-Ala-OH] 2 [S-S] (see Fig. 1), in which the two cysteines form a disulfide bond that covalently links the two 3A ends of the oligonucleotide moiety. The DNA sequence is self-complementary, and the peptide is long enough to allow for the crosslinking of the two cys...

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Conformation of the circular dumbbell d〈pCGC-TT-GCG-TT〉: Structure determination and molecular dynamics

Cited by 28 publications

References 65 publications

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

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

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

Solution structure and stability of a disulfide cross-linked nucleopeptide duplex

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