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

Acta Crystallogr D Biol Crystallogr. 2003 Aug;59(Pt 8):1525-8. doi: 10.1107/s0907444903012381. Epub 2003 Jul 23.

Abstract

The first antiviral nucleoside 5-iodo-2'-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 self-complementary 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. Refinement in the resolution range 20-1.3 A converged with a final 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 IDU.A 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cobalt / chemistry
  • DNA, Z-Form / chemistry*
  • Humans
  • Idoxuridine / chemistry*
  • Models, Molecular
  • Nucleic Acid Conformation
  • Nucleosides / chemistry*
  • Thymidine Kinase / chemistry
  • X-Ray Diffraction

Substances

  • DNA, Z-Form
  • Nucleosides
  • hexaamminecobalt(II)
  • Cobalt
  • Thymidine Kinase
  • Idoxuridine