Exploration of the influence of 5-iodo-2′-deoxyuridine incorporation on the structure of d[CACG(IDU)G]

Abstract

The ®rst antiviral nucleoside 5-iodo-2 H -deoxyuridine (IDU) against herpes simplex virus type 1 and type 2 is a thymidine analogue, i.e. the C5 methyl group is replaced by an I atom. The structure of the selfcomplementary hexamer d[CACG(IDU)G] was determined by single-crystal X-ray diffraction techniques. The orthorhombic crystals belong to space group P2 1 2 1 2 1 , with unit-cell parameters a = 18.16, b = 30.03, c = 41.99 A Ê . Re®nement in the resolution range 20±1.3 A Ê converged with a ®nal R1 = 0.167, including 43 water molecules and two cobalt hexammine complexes. The incorporation of a large I atom has only minor consequences for the overall structure as is noticed in the IDUÁA base pairs, which are of the common Watson± Crick type. To contribute to the still puzzling mechanism of this historically important agent, details of base stacking, helical parameters, hydration etc. have been studied. A general scheme of cobalt hexammine-binding modes in Z-DNA is provided, revealing similar binding modes for the reported structure.

A Comprehensive Ab Initio Study of Halogenated A···U and G···C Base Pair Geometries and Energies

“…As the final stage of our study, we selected several representative examples from the PDB search and evaluated the stability of halogenated BPs (three of them are shown in Figure 9 ). The selected examples involved a distorted DNA structure ( Figure 9 a, PDBID: 1OMK) [ 41 ] corresponding to the first antiviral nucleoside 5-iodo-2’-deoxyuridine (IDU) against herpes simplex virus type 1 and type 2 and two protein-DNA complexes, which involve a THAP-family C(2)CH zinc-coordinating DNA-binding protein ( Figure 9 b, PDBID: 3KDE) [ 42 ] and the Bacillus halodurans RNase H ( Bh RNase H) protein ( Figure 9 c, PDBID: 4HUG) [ 43 ].…”

High-resolution crystal structure of Z-DNA in complex with Cr3+ cations

“…As described in detail by Brzezinski et al [ 29 ], d(CGCGCG) 2 Z-DNA crystallizes into two polymorphic forms (A and B) of the same space group and cell parameters, but with different crystal packing. A detailed discussion of the influence of metal and/or polyamine cations, and disorder of Z-DNA on crystal packing can be found in Brzezinski et al [ 29 ], Schuerman et al [ 37 ] and Harper et al [ 38 ].…”

“…The crystal structure of the d(CGCGCG) 2 –Cr 3+ complex analyzed in this study has the same packing mode of the Z-DNA helices as the d(CACGIUG) 2 –[Co(NH 3 ) 6 ] 3+ (PDB 1omk) [ 37 ] and d(TGCGCA) 2 –[Co(NH 3 ) 6 ] 3+ (362d) structures [ 38 ]. Although sperminium tetrachloride was present in the crystallization conditions, the spermine 4+ tetracation has not been identified in the electron density maps of the d(CGCGCG) 2 –Cr 3+ crystal.…”

Phosphates in the Z-DNA dodecamer are flexible, but their P-SAD signal is sufficient for structure solution

“…The following references are cited in the Supporting Information: Wang et al (1981Wang et al ( , 1984, Tereshko et al (2001), Narayana et al (2006), Egli et al (1991), Bancroft et al (1994), Chatake et al (2005), Schuerman et al (2003), Thiyagarajan et al (2002Thiyagarajan et al ( , 2004, Harper et al (1998), Van Meervelt et al (1990, Moore et al (1995), Brzezinski et al (2011), Dauter & Adamiak (2001), Drozdzal et al (2013), Ohishi et al (1991Ohishi et al ( , 2002Ohishi et al ( , 2007Ohishi et al ( , 2008, Gessner et al (1989), Wilds et al (2002), Coll et al (1986Coll et al ( , 1989, Sanishvili et al (2007), , Ohishi, Terasoma et al (1996), Fenn et al (2011), Pan & Sundaralingam (2003), Ho et al (1985), Brown et al (1986), Schuerman et al (1998), Bharanidharan et al (2007), Sadasivan & Gautham (1995), Karthe & Gautham (1998), Kagawa et al (1991), Fujii et al (1982), Chevrier et al (1986), Geierstanger et al (1991), Zhou & Ho (1990), Ginell et al (1990),…”