Field- and phage-Induced dipolar couplings in a homodimeric DNA quadruplex: Relative orientation of G·(C-A) triad and G-Tetrad motifs and direct determination of C2 symmetry axis orientation Journal Article


Authors: Al-Hashimi, H. M.; Majumdar, A.; Gorin, A.; Kettani, A.; Skripkin, E.; Patel, D. J.
Article Title: Field- and phage-Induced dipolar couplings in a homodimeric DNA quadruplex: Relative orientation of G·(C-A) triad and G-Tetrad motifs and direct determination of C2 symmetry axis orientation
Abstract: We present a new NMR procedure for determining the three-Dimensional fold of C2-Symmetric nucleic acid homodimers that relies on long-range orientational constraints derived from the measurement of two independent sets of residual dipolar couplings under two alignment conditions. The application is demonstrated on an 15N/13C-Enriched deoxyoligonucleotide sequence, d(G-G-G-T-T-C-A-G-G), shown previously to dimerize into a quadruplex in solution and form a pair of G·(C-A) triads and G-G-G-G tetrads (G-Tetrad) motifs. One-bond 1H-15N (1DNH) and 1H13C (1DCH) residual dipolar couplings have been measured between nuclei in the bases of these motifs using bacteriophage as an ordering medium, and under direct magnetic field alignment (800 MHz). By combining the two dipolar data sets in an order matrix analysis, the orientation of the G·(C-A) triad relative to the G-tetrad within a contiguous monomeric unit can directly be determined, even in the presence of interstrand/intrastrand NOE ambiguity. We further demonstrate that the orientation of the C2-Axis of molecular symmetry in the homodimer relative to the G·(C-A) triad and G-tetrad motifs can unambiguously be determined using the two sets of independent dipolar coupling measurements. The three-dimensional fold of the homodimer determined using this procedure is very regular and in excellent agreement with a previously determined high-Resolution NOE-Based NMR structure, where interstrand/intrastrand NOEs were treated as ambiguous and where noncrystallographic symmetry constraints were implicitly imposed during the structure calculation.
Keywords: dna; nucleotide sequence; base pairing; dna structure; hydrogen bonding; dimerization; conformational transition; nuclear magnetic resonance; oligodeoxynucleotide; magnetics; nucleic acid; hydrogen; dna conformation; nuclear magnetic resonance, biomolecular; chemical binding; dna strand; carbon 13; nitrogen 15; article
Journal Title: Journal of the American Chemical Society
Volume: 123
Issue: 4
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 2001-01-31
Start Page: 633
End Page: 640
Language: English
DOI: 10.1021/ja003379y
PUBMED: 11456575
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Andrey A Gorin
    25 Gorin
  2. Dinshaw J Patel
    392 Patel