Conformational perturbation of the anticancer nucleoside arabinosylcytosine on Z‐DNA: Molecular structure of (araC‐dG)3 at 1.3 Å resolution

Hong Zhang, Gijs A. Van Der Marel, Jacques H. Van Boom, Andrew H.‐J Wang

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

The left‐handed Z‐DNA structure of an araC‐containing (where araC stands for arabinosylcytosine) hexamer, (araC‐dG)3, has been solved by x‐ray diffraction analysis at 1.3 A resolution. This hexamer was crystallized in the hexagonal P6522 (a = b = 17.96 Å, c = 43.22 Å) space group in which the hexamers have statistically disordered packing arrangement along the 65 screw axis, yet the crystals diffract x‐rays to high resolution. Its structure has been refined by the constrained least square refinement to a final R factor of 0.287 using 737 [> 3.0 σ(F)] observed reflections. The asymmetric unit of the unit cell contains only a dinucleotide, 5′‐p(araC)p(dG). The overall conformation resembles that of the canonical Z‐DNA, but with some differences in details. The O2′ hydroxyl groups of the araC residues form intramolecular hydrogen bonds with N2 of the 5′‐guanine residues. In the deep groove of Z‐DNA, these hydroxy groups replace the bridging water molecules that stabilize the guanine in the syn conformation. The results reinforce the earlier observation made by the structural analysis of another hexamer, d(CG[araC]GCG), with a mono‐substitution of araC [M.‐K. Teng, Y.‐C. Liaw, G. A. van der Marel, J. H. van Boom, and A. H.‐J. Wang (1989) Biochemistry, vol. 28, pp. 4923–4928]. These two structures show that araC residue can be incorporated readily into the Z structure and probably facilitates the B to Z transition, as supported by uv absorption spectroscopic studies in a number of araC‐containing oligonucleotides. The potential biological roles of the araC‐modified Z‐DNA are discussed. © 1992 John Wiley & Sons, Inc.

原文英語
頁(從 - 到)1559-1569
頁數11
期刊Biopolymers
32
發行號11
DOIs
出版狀態已發佈 - 11月 1992
對外發佈

ASJC Scopus subject areas

  • 生物物理學
  • 生物化學
  • 生物材料
  • 有機化學

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