Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Jun 15;26(12):2873–2878. doi: 10.1093/nar/26.12.2873

Visualisation of extensive water ribbons and networks in a DNA minor-groove drug complex.

A Guerri 1, I J Simpson 1, S Neidle 1
PMCID: PMC147633  PMID: 9611230

Abstract

The crystal structure is reported of a complex between an ethyl derivative of the minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2, which has been refined to 1.85 A resolution and an R factor of 16.6% for data collected at -173 degreesC. An exceptionally large number (220) of water molecules have been located. The majority of these occur in the first coordination shell of solvation. There are extensive networks of connected waters, both in the major and minor grooves. In particular, there are 21 water molecules associated with the minor-groove drug, via hydrogen bonds from the four charged nitrogen atoms. One cluster of four waters is situated in the groove itself; the majority are on the outer edge of the groove, and serve to bridge between the outward-directed drug nitrogen atoms and backbone phosphate oxygen atoms. These bridges are both intra- and inter-strand, with the net effect that the outer edge of the drug molecule is covered by ribbons of water molecules.

Full Text

The Full Text of this article is available as a PDF (234.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Billeter M., Güntert P., Luginbühl P., Wüthrich K. Hydration and DNA recognition by homeodomains. Cell. 1996 Jun 28;85(7):1057–1065. doi: 10.1016/s0092-8674(00)81306-9. [DOI] [PubMed] [Google Scholar]
  2. Boykin D. W., Kumar A., Spychala J., Zhou M., Lombardy R. J., Wilson W. D., Dykstra C. C., Jones S. K., Hall J. E., Tidwell R. R. Dicationic diarylfurans as anti-Pneumocystis carinii agents. J Med Chem. 1995 Mar 17;38(6):912–916. doi: 10.1021/jm00006a009. [DOI] [PubMed] [Google Scholar]
  3. Boykin D. W., Kumar A., Xiao G., Wilson W. D., Bender B. C., McCurdy D. R., Hall J. E., Tidwell R. R. 2,5-bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents. J Med Chem. 1998 Jan 1;41(1):124–129. doi: 10.1021/jm970570i. [DOI] [PubMed] [Google Scholar]
  4. Brown D. G., Sanderson M. R., Garman E., Neidle S. Crystal structure of a berenil-d(CGCAAATTTGCG) complex. An example of drug-DNA recognition based on sequence-dependent structural features. J Mol Biol. 1992 Jul 20;226(2):481–490. doi: 10.1016/0022-2836(92)90962-j. [DOI] [PubMed] [Google Scholar]
  5. Brown D. G., Sanderson M. R., Skelly J. V., Jenkins T. C., Brown T., Garman E., Stuart D. I., Neidle S. Crystal structure of a berenil-dodecanucleotide complex: the role of water in sequence-specific ligand binding. EMBO J. 1990 Apr;9(4):1329–1334. doi: 10.1002/j.1460-2075.1990.tb08242.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brünger A. T., Kuriyan J., Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. doi: 10.1126/science.235.4787.458. [DOI] [PubMed] [Google Scholar]
  7. Chalikian T. V., Plum G. E., Sarvazyan A. P., Breslauer K. J. Influence of drug binding on DNA hydration: acoustic and densimetric characterizations of netropsin binding to the poly(dAdT).poly(dAdT) and poly(dA).poly(dT) duplexes and the poly(dT).poly(dA).poly(dT) triplex at 25 degrees C. Biochemistry. 1994 Jul 26;33(29):8629–8640. doi: 10.1021/bi00195a003. [DOI] [PubMed] [Google Scholar]
  8. Chiang S. Y., Welch J., Rauscher F. J., 3rd, Beerman T. A. Effects of minor groove binding drugs on the interaction of TATA box binding protein and TFIIA with DNA. Biochemistry. 1994 Jun 14;33(23):7033–7040. doi: 10.1021/bi00189a003. [DOI] [PubMed] [Google Scholar]
  9. Drew H. R., Dickerson R. E. Structure of a B-DNA dodecamer. III. Geometry of hydration. J Mol Biol. 1981 Sep 25;151(3):535–556. doi: 10.1016/0022-2836(81)90009-7. [DOI] [PubMed] [Google Scholar]
  10. Duan Y., Wilkosz P., Crowley M., Rosenberg J. M. Molecular dynamics simulation study of DNA dodecamer d(CGCGAATTCGCG) in solution: conformation and hydration. J Mol Biol. 1997 Oct 3;272(4):553–572. doi: 10.1006/jmbi.1997.1247. [DOI] [PubMed] [Google Scholar]
  11. Dunitz J. D. The entropic cost of bound water in crystals and biomolecules. Science. 1994 Apr 29;264(5159):670–670. doi: 10.1126/science.264.5159.670. [DOI] [PubMed] [Google Scholar]
  12. Ladbury J. E. Just add water! The effect of water on the specificity of protein-ligand binding sites and its potential application to drug design. Chem Biol. 1996 Dec;3(12):973–980. doi: 10.1016/s1074-5521(96)90164-7. [DOI] [PubMed] [Google Scholar]
  13. Laughton C. A., Tanious F., Nunn C. M., Boykin D. W., Wilson W. D., Neidle S. A crystallographic and spectroscopic study of the complex between d(CGCGAATTCGCG)2 and 2,5-bis(4-guanylphenyl)furan, an analogue of berenil. Structural origins of enhanced DNA-binding affinity. Biochemistry. 1996 May 7;35(18):5655–5661. doi: 10.1021/bi952162r. [DOI] [PubMed] [Google Scholar]
  14. Liepinsh E., Otting G., Wüthrich K. NMR observation of individual molecules of hydration water bound to DNA duplexes: direct evidence for a spine of hydration water present in aqueous solution. Nucleic Acids Res. 1992 Dec 25;20(24):6549–6553. doi: 10.1093/nar/20.24.6549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marky L. A., Breslauer K. J. Origins of netropsin binding affinity and specificity: correlations of thermodynamic and structural data. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4359–4363. doi: 10.1073/pnas.84.13.4359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Neidle S., Berman H. M., Shieh H. S. Highly structured water network in crystals of a deoxydinucleoside---drug complex. Nature. 1980 Nov 13;288(5787):129–133. doi: 10.1038/288129a0. [DOI] [PubMed] [Google Scholar]
  17. Nunn C. M., Jenkins T. C., Neidle S. Crystal structure of d(CGCGAATTCGCG) complexed with propamidine, a short-chain homologue of the drug pentamidine. Biochemistry. 1993 Dec 21;32(50):13838–13843. doi: 10.1021/bi00213a012. [DOI] [PubMed] [Google Scholar]
  18. Nunn C. M., Jenkins T. C., Neidle S. Crystal structure of gamma-oxapentamidine complexed with d(CGCGAATTCGCG)2. The effects of drug structural change on DNA minor-groove recognition. Eur J Biochem. 1994 Dec 15;226(3):953–961. doi: 10.1111/j.1432-1033.1994.00953.x. [DOI] [PubMed] [Google Scholar]
  19. Nunn C. M., Neidle S. Sequence-dependent drug binding to the minor groove of DNA: crystal structure of the DNA dodecamer d(CGCAAATTTGCG)2 complexed with propamidine. J Med Chem. 1995 Jun 23;38(13):2317–2325. doi: 10.1021/jm00013a008. [DOI] [PubMed] [Google Scholar]
  20. Parkinson G., Vojtechovsky J., Clowney L., Brünger A. T., Berman H. M. New parameters for the refinement of nucleic acid-containing structures. Acta Crystallogr D Biol Crystallogr. 1996 Jan 1;52(Pt 1):57–64. doi: 10.1107/S0907444995011115. [DOI] [PubMed] [Google Scholar]
  21. Rentzeperis D., Marky L. A., Dwyer T. J., Geierstanger B. H., Pelton J. G., Wemmer D. E. Interaction of minor groove ligands to an AAATT/AATTT site: correlation of thermodynamic characterization and solution structure. Biochemistry. 1995 Mar 7;34(9):2937–2945. doi: 10.1021/bi00009a025. [DOI] [PubMed] [Google Scholar]
  22. Saenger W., Hunter W. N., Kennard O. DNA conformation is determined by economics in the hydration of phosphate groups. 1986 Nov 27-Dec 3Nature. 324(6095):385–388. doi: 10.1038/324385a0. [DOI] [PubMed] [Google Scholar]
  23. Schneider B., Cohen D., Berman H. M. Hydration of DNA bases: analysis of crystallographic data. Biopolymers. 1992 Jul;32(7):725–750. doi: 10.1002/bip.360320703. [DOI] [PubMed] [Google Scholar]
  24. Seeman N. C., Rosenberg J. M., Rich A. Sequence-specific recognition of double helical nucleic acids by proteins. Proc Natl Acad Sci U S A. 1976 Mar;73(3):804–808. doi: 10.1073/pnas.73.3.804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Trent J. O., Clark G. R., Kumar A., Wilson W. D., Boykin D. W., Hall J. E., Tidwell R. R., Blagburn B. L., Neidle S. Targeting the minor groove of DNA: crystal structures of two complexes between furan derivatives of berenil and the DNA dodecamer d(CGCGAATTCGCG)2. J Med Chem. 1996 Nov 8;39(23):4554–4562. doi: 10.1021/jm9604484. [DOI] [PubMed] [Google Scholar]
  26. Wood A. A., Nunn C. M., Czarny A., Boykin D. W., Neidle S. Variability in DNA minor groove width recognised by ligand binding: the crystal structure of a bis-benzimidazole compound bound to the DNA duplex d(CGCGAATTCGCG)2. Nucleic Acids Res. 1995 Sep 25;23(18):3678–3684. doi: 10.1093/nar/23.18.3678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zimmer C., Wähnert U. Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Prog Biophys Mol Biol. 1986;47(1):31–112. doi: 10.1016/0079-6107(86)90005-2. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES