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Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
June 17-21 2003

Cation-π Interactions at Protein-DNA Interfaces: Possible Role in the Charge Migration Along the DNA Stack

The role of cation-π interactions at the interface of protein-DNA complexes has been investigated by means of ab initio quantum mechanics energy calculations and X-ray structure analyses. The most frequently observed cation-π pair, which is also the most stable as monitored by MP2 energy calculations in vacuum, is Arg-guanine. These interactions often occur concomitantly with H-bonds, which led us to define stair-shaped recurrent motifs. These consist of two successive bases along the DNA stack, one in cation-π interaction with an amino acid side-chain (Arg, Lys, Asn, Gln), and the other H-bonded with the same side-chain. They are sometimes part of larger motifs, containing several successive stairs. In other extended motifs, termed cation-π chain motifs, an amino acid side-chain or a nucleic acid base forms simultaneously two cation-π interactions. Such motifs are for instance encountered in proteins that expulse a base from the DNA stack and replace it by an amino acid side-chain, which forms cation-π interactions with the two neighboring bases along the DNA strand.


An H-bond/cation-π stair motif. The geometry is taken from the X-ray structure of tc3 transposase (protein code 1TC3) and the interacting residues are Arg-C236, Gua-A7 and Gua-A8. Atoms O, N, C and H are colored in red, blue, black and grey, respectively. The image was generated using Insight II (Accelrys Inc.).

The striking conservation of typical stair and cation-π chain motifs within families of protein/DNA complexes suggests that they might play a structural and/or functional role. They might moreover influence electron migration through the DNA double helix. Indeed, the insertion of a positively charged amino acid between stacked nucleic acid bases should have a repulsive action on electron holes and hence should prevent their migration through the DNA portion bound to this amino acid. Furthermore, if electron holes migrate along a given DNA duplex, they tend to be localized on several consecutive guanines. Since most of the protein/DNA binding sites involve guanines, these sites are likely to contain an electron hole. The presence of this hole, it can be argued, should modify the affinity of DNA-binding proteins for their DNA target, especially if these proteins need to form cation-π interactions with DNA bases. Hence, we may assume that DNA-binding proteins with cation-π interactions recognize not only specific DNA sequences but DNA binding sequences with specific charge properties.

Christophe Biot1,*
René Wintjens2
Eric Buisine3
Jacky Liévin4
Marianne Rooman1

1Ingénierie Moléculaire et Biomoléculaire
Université Libre de Bruxelles
CP 165/64
50 Avenue F.D. Roosevelt
B-1050 Bruxelles, Belgium
2Université Libre de Bruxelles
Institut de Pharmacie
Chimie Générale, CP 206/4
Campus de la Plaine
Boulevard du Triomphe
1050 Bruxelles, Belgium
3Laboratoire de Chimie Organique et Macromoléculaire
UPRESA-CNRS 8009
Université des Sciences et Technologies de Lille
59655 Villeneuve d'Ascq Cedex, France
4Université Libre de Bruxelles
Laboratoire de Chimie Physique Moléculaire
Cp 160/09
50 Avenue F.D. Roosevelt
B-1050 Bruxelles, Belgium
*Phone: (+32)-2-650 3001
Fax: (+32)-2-650 3606
cbiot@ulb.ac.be