Abstract
The X-ray crystal structure of the d(CGCGCG)2/putrescine(2+)/K+ complex has been determined at 0.60 Å resolution. Stereochemical restraints were used only for the putrescinium dication, and 23 bonds and 18 angles of the Z-DNA nucleotides with dual conformation. The N atoms of the putrescine(2+) dication form three direct hydrogen bonds with the N7_G atoms of three different Z-DNA molecules, plus three water-mediated hydrogen bonds with cytosine, guanine and phosphate acceptors. A unique potassium cation was also unambiguously identified in the structure, albeit at a ∼0.5 occupation site shared with a water molecule, providing the first example of such a complex with Z-DNA. The K+ cation has coordination number of eight and an irregular coordination sphere, formed by four water molecules and four O atoms from two phosphate groups of the Z-DNA, including ligands present at fractional occupancy. The structural disorder of the Z-DNA duplex is manifested by the presence of alternate conformations along the DNA backbone. Comparison of the position and interactions of putrescine(2+) in the present structure with other ultra-high-resolution structures of Z-DNA in complexes with Mn2+ and Zn2+ ions shows that the dicationic putrescinium moiety can effectively substitute these metal ions for stabilization of Z-type DNA duplexes. Furthermore, this comparison also suggests that the spermine(4+) tetracation has a higher affinity for Z-DNA than K+.
Highlights
Biogenic polyamine cations are essential for cell growth and differentiation, and their biochemical significance in a wide spectrum of physiological functions has been repeatedly reviewed (Gugliucci, 2004; Moinard et al, 2005; Larqueet al., 2007; Igarashi & Kashiwagi, 2010; Jastrzab et al, 2016)
The agreement with stereochemical standards (r.m.s.d.) is 0.010 Afor bond lengths and 1.56 for bond angles. These results are comparable in terms of accuracy and precision with the record-setting model of Z-DNA (0.55 A, R = 7.77%, Protein Data Bank (PDB) ID 3p4j) described by Brzezinski et al (2011)
We have presented a new crystal structure of Z-DNA/polyamine(n+), in complex with putrescine(2+) and K+ cations
Summary
Biogenic polyamine cations are essential for cell growth and differentiation, and their biochemical significance in a wide spectrum of physiological functions has been repeatedly reviewed (Gugliucci, 2004; Moinard et al, 2005; Larqueet al., 2007; Igarashi & Kashiwagi, 2010; Jastrzab et al, 2016). Common compounds in this group include the diamines 1,3diaminopropane(2+) (Dap2+), putrescine(2+) (Put2+) and cadaverine(2+) (Cad2+), the triamines spermidine(3+) (Spd3+) and norspermidine(3+), and the tetramine spermine(4+) (Spm4+). The cations are coordinated simultaneously by the guanine bases from different helices and by the O atoms of dual-conformation phosphate groups (Tomita et al, 1989; Gao et al, 1993)
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