Solution structure of two mismatches G·G and I·I in the K-ras gene context by nuclear magnetic resonance and molecular dynamics

Valerie Faibis, Jean A H Cognet, Yves Boulard, Lawrence Sowers, G. Victor Fazakerley

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Two mismatches, G·G and I·I, have been incorporated at the central position of 5'd(GCCACXAGCTC)·d(GAGCTXGTGGC) in order to carry out NMR and molecular dynamics studies. These duplexes constitute the sequence 29-39 of the K-ras gene coding for the glycine 12, a hot spot for mutation. The NMR spectra show that the duplexes are not greatly distorted by the introduction of the mismatches and their global conformation is that of a canonical B- form double helix. For the duplex containing the G·G mismatch, we propose for the major species, a type of pairing involving one hydrogen bond between the imino group of one central guanine and the carbonyl group of the opposite guanine. Both bases are in an anti conformation. Two conformations, with the same donor and acceptor pattern can coexist, one is obtained from the other by a 180° rotation about the pseudodyadic axis. Exchange between the two forms is observed by NMR at low temperature. A minor species involving hydrogen bonding between the guanine amino group and the carbonyl group of the guanine on the opposite strand may also exist as shown by the molecular dynamics calculations. For the I·I mismatch we observe the same major species, i.e., hydrogen bonding between an imino proton of one base and the carbonyl group of the base on the opposite strand with both bases in an anti conformation. Exchange between these two conformations is faster than for the G·G mismatch. Further, we observe that the I·I mismatch adopts a minor conformation, in which one or other of the bases is in the syn conformation.

Original languageEnglish (US)
Pages (from-to)14452-14464
Number of pages13
JournalBiochemistry
Volume35
Issue number46
DOIs
StatePublished - Nov 19 1996
Externally publishedYes

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ras Genes
Guanine
Molecular Dynamics Simulation
Conformations
Molecular dynamics
Magnetic Resonance Spectroscopy
Genes
Nuclear magnetic resonance
Hydrogen Bonding
Hydrogen bonds
Glycine
Protons
Hydrogen
Mutation
Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

Solution structure of two mismatches G·G and I·I in the K-ras gene context by nuclear magnetic resonance and molecular dynamics. / Faibis, Valerie; Cognet, Jean A H; Boulard, Yves; Sowers, Lawrence; Fazakerley, G. Victor.

In: Biochemistry, Vol. 35, No. 46, 19.11.1996, p. 14452-14464.

Research output: Contribution to journalArticle

Faibis, Valerie ; Cognet, Jean A H ; Boulard, Yves ; Sowers, Lawrence ; Fazakerley, G. Victor. / Solution structure of two mismatches G·G and I·I in the K-ras gene context by nuclear magnetic resonance and molecular dynamics. In: Biochemistry. 1996 ; Vol. 35, No. 46. pp. 14452-14464.
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