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Title: Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.

Abstract

Magnesium ions play important roles in the structure and function of nucleic acids. Whereas the tertiary folding of RNA often requires magnesium ions binding to tight places where phosphates are clustered, the molecular basis of the interactions of magnesium ions with RNA helical regions is less well understood. We have refined the crystal structures of four decamer oligonucleotides, d(ACCGGCCGGT), r(GCG)d(TATACGC), r(GC)d(GTATACGC) and r(G)d(GCGTATACGC) with bound hexahydrated magnesium ions at high resolution. The structures reveal that A-form nucleic acid has characteristic [Mg(H2O)6]2+ binding modes. One mode has the ion binding in the deep major groove of a GpN step at the O6/N7 sites of guanine bases via hydrogen bonds. Our crystallographic observations are consistent with the recent NMR observations that in solution [Co(NH3)6]3+, a model ion of [Mg(H2O)6]2+, binds in an identical manner. The other mode involves the binding of the ion to phosphates, bridging across the outer mouth of the narrow major groove. These [Mg(H2O)6]2+ ions are found at the most negative electrostatic potential regions of A-form duplexes. We propose that these two binding modes are important in the global charge neutralization, and therefore stability, of A-form duplexes.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC)
OSTI Identifier:
949607
Report Number(s):
ANL/BIO/JA-42482
Journal ID: ISSN 0305-1048; NARHAD; TRN: US201012%%391
DOE Contract Number:
DE-AC02-06CH11357
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nucleic Acids Res.; Journal Volume: 28; Journal Issue: 8 ; 2000
Country of Publication:
United States
Language:
ENGLISH
Subject:
08 HYDROGEN; 36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; ELECTROSTATICS; GUANINE; HYDROGEN; MAGNESIUM IONS; NUCLEIC ACIDS; OLIGONUCLEOTIDES; PHOSPHATES; RESOLUTION; RNA; STABILITY

Citation Formats

Robinson, H., Gao, Y.-G., Sanishvili, R., Joachimiak, A., Wang, A. H.-J., Univ. of Illinois, and Northwestern Univ. Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.. United States: N. p., 2000. Web. doi:10.1093/nar/28.8.1760.
Robinson, H., Gao, Y.-G., Sanishvili, R., Joachimiak, A., Wang, A. H.-J., Univ. of Illinois, & Northwestern Univ. Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.. United States. doi:10.1093/nar/28.8.1760.
Robinson, H., Gao, Y.-G., Sanishvili, R., Joachimiak, A., Wang, A. H.-J., Univ. of Illinois, and Northwestern Univ. 2000. "Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.". United States. doi:10.1093/nar/28.8.1760.
@article{osti_949607,
title = {Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes.},
author = {Robinson, H. and Gao, Y.-G. and Sanishvili, R. and Joachimiak, A. and Wang, A. H.-J. and Univ. of Illinois and Northwestern Univ.},
abstractNote = {Magnesium ions play important roles in the structure and function of nucleic acids. Whereas the tertiary folding of RNA often requires magnesium ions binding to tight places where phosphates are clustered, the molecular basis of the interactions of magnesium ions with RNA helical regions is less well understood. We have refined the crystal structures of four decamer oligonucleotides, d(ACCGGCCGGT), r(GCG)d(TATACGC), r(GC)d(GTATACGC) and r(G)d(GCGTATACGC) with bound hexahydrated magnesium ions at high resolution. The structures reveal that A-form nucleic acid has characteristic [Mg(H2O)6]2+ binding modes. One mode has the ion binding in the deep major groove of a GpN step at the O6/N7 sites of guanine bases via hydrogen bonds. Our crystallographic observations are consistent with the recent NMR observations that in solution [Co(NH3)6]3+, a model ion of [Mg(H2O)6]2+, binds in an identical manner. The other mode involves the binding of the ion to phosphates, bridging across the outer mouth of the narrow major groove. These [Mg(H2O)6]2+ ions are found at the most negative electrostatic potential regions of A-form duplexes. We propose that these two binding modes are important in the global charge neutralization, and therefore stability, of A-form duplexes.},
doi = {10.1093/nar/28.8.1760},
journal = {Nucleic Acids Res.},
number = 8 ; 2000,
volume = 28,
place = {United States},
year = 2000,
month = 1
}
  • Complementary base-paired polynucleotide duplexes are quite polymorphic. This is not surprising when one considers that the shape of their usual unit of structure, the nucleotide, has six endocyclic bonds and a fairly flexible furanose ring with which to contrive changes in shape. These different residue shapes confer very distinctive morphologies on the polymer helices which incorporate them. These differences are indicated by the axial translation (h) and rotation (t) per nucleotide residue in each helix.
  • No abstract prepared.
  • We have studied the conformational effects of 4-aminobiphenyl modification at C-8 of guanine or adenine on double-stranded DNA trimers. We used sequences with the modified purine at the central base pair and all 16 possible neighboring sequences at the outer pairs. Minimized potential energy calculations were carried out using the molecular mechanics program DUPLEX to survey the conformation space of these adducts, using a total of 1280 starting structures both in the modified guanine series and in the modified adenine series. Conformer families in which the bound 4-aminobiphenyl was located in the DNA major groove, and in the minor groove,more » were located for both adenine and guanine modification. In the modified guanine series, the major and minor groove families were roughly comparable in energy, and the sequence context determined which was more stable in a particular case. In the modified adenine series, however, the minor groove structure was more that 10 kcal/mol more stable than the major groove for all sequences. As a result, minor groove adducts provided most of the global minima in the adenine-modified series. This result may be relevant to a previous mutagenesis study [Lasko et al. (1988) J. Biol. Chem. 263, 15429-15435] in which the hot spot of most frequent occurrence was located at an adenine, in the sequence GAT. 25 refs., 9 figs., 4 tabs.« less
  • Geometric descriptions of nonideal interresidue hydrogen bonding and backbone-base water bridging in the minor groove are established in terms of polyamide backbone carbonyl group orientation from analyses of residue junction conformers in experimentally determined peptide nucleic acid (PNA) complexes. Two types of interresidue hydrogen bonding are identified in PNA conformers in heteroduplexes with nucleic acids that adopt A-like base pair stacking. Quantum chemical calculations on the binding of a water molecule to an O2 base atom in glycine-based PNA thymine dimers indicate that junctions modeled with P-form backbone conformations are lower in energy than a dimer comprising the predominant conformationmore » observed in A-like helices. It is further shown in model systems that PNA analogs based on D-lysine are better able to preorganize in a conformation exclusive to P-form helices than is glycine-based PNA. An intrinsic preference for this conformation is also exhibited by positively charged chiral PNA dimers carrying 3-amino-D-alanine or 4-aza-D-leucine residue units that provide for additional rigidity by side-chain hydrogen bonding to the backbone carbonyl oxygen. Structural modifications stabilizing P-form helices may obviate the need for large heterocycles to target DNA pyrimidine bases via PNADNA-PNA triplex formation. Quantum chemical modeling methods are used to propose candidate PNA Hoogsteen strand designs.« less