Effects of 5-fluorouracil/guanine wobble base pairs in Z-DNA: Molecular and crystal structure of d(CGCGFG)

Miquel Coll, Daniel Saal, Christin A. Frederick, Juan Aymami, Alexander Rich, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)


The chemotherapeutic agent 5-fluorouracil is a DNA base analogue which is known to incorporate Into DNA in vivo. We have solved the structure of the oligonucleotide d(CGCGFG), where F is 5-fluorouracil (5FU). The DNA hexamer crystallizes in the Z-DNA conformation at two pH values with the 5FU forming a wobble base pair with guanine In both crystal forms. No evidence of the enol or ionized form of 5FU is found under either condition. The crystals diffracted X-rays to a resolution of 1.5 A and their structures have been refined to R-factors of 20.0% and 17.2%, respectively, for the pH-7.0 and pH-9.0 forms. By comparing this structure to that of d(CGCGCG) and d(CGCGTG), we were able to demonstrate that the backbone conformation of d(CGCGFG) is similar to that of the archetypal Z-DNA. The two F-G wobble base pairs in the duplex are structurally similar to the T-G base pairs both with respect to the DNA helix itself and its interactions with solvent molecules. In both cases water molecules associated with the wobble base pairs bridge between the bases and stabilize the structure. The fluorine in the 5FU base is hydrophobic and is not hydrogen bonded to any solvent molecules.

Original languageEnglish
Pages (from-to)911-923
Number of pages13
JournalNucleic Acids Research
Issue number3
Publication statusPublished - Feb 11 1989
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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