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
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