Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Aug 15;89(16):7586–7590. doi: 10.1073/pnas.89.16.7586

Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2-carboxamide netropsin.

M Mrksich 1, W S Wade 1, T J Dwyer 1, B H Geierstanger 1, D E Wemmer 1, P B Dervan 1
PMCID: PMC49755  PMID: 1323845

Abstract

The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5'-TGACT-3'. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.

Full text

PDF
7586

Images in this article

7589Image
on p.7589
7590Image
on p.7590

Selected References

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

  1. Coll M., Frederick C. A., Wang A. H., Rich A. A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8385–8389. doi: 10.1073/pnas.84.23.8385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gao X. L., Patel D. J. Solution structure of the chromomycin-DNA complex. Biochemistry. 1989 Jan 24;28(2):751–762. doi: 10.1021/bi00428a051. [DOI] [PubMed] [Google Scholar]
  3. Hare D. R., Wemmer D. E., Chou S. H., Drobny G., Reid B. R. Assignment of the non-exchangeable proton resonances of d(C-G-C-G-A-A-T-T-C-G-C-G) using two-dimensional nuclear magnetic resonance methods. J Mol Biol. 1983 Dec 15;171(3):319–336. doi: 10.1016/0022-2836(83)90096-7. [DOI] [PubMed] [Google Scholar]
  4. Kissinger K., Krowicki K., Dabrowiak J. C., Lown J. W. Molecular recognition between oligopeptides and nucleic acids. Monocationic imidazole lexitropsins that display enhanced GC sequence dependent DNA binding. Biochemistry. 1987 Sep 8;26(18):5590–5595. doi: 10.1021/bi00392a002. [DOI] [PubMed] [Google Scholar]
  5. Klevit R. E., Wemmer D. E., Reid B. R. 1H NMR studies on the interaction between distamycin A and a symmetrical DNA dodecamer. Biochemistry. 1986 Jun 3;25(11):3296–3303. doi: 10.1021/bi00359a032. [DOI] [PubMed] [Google Scholar]
  6. Kopka M. L., Yoon C., Goodsell D., Pjura P., Dickerson R. E. Binding of an antitumor drug to DNA, Netropsin and C-G-C-G-A-A-T-T-BrC-G-C-G. J Mol Biol. 1985 Jun 25;183(4):553–563. doi: 10.1016/0022-2836(85)90171-8. [DOI] [PubMed] [Google Scholar]
  7. Kopka M. L., Yoon C., Goodsell D., Pjura P., Dickerson R. E. The molecular origin of DNA-drug specificity in netropsin and distamycin. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1376–1380. doi: 10.1073/pnas.82.5.1376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lee M., Chang D. K., Hartley J. A., Pon R. T., Krowicki K., Lown J. W. Structural and dynamic aspects of binding of a prototype lexitropsin to the decadeoxyribonucleotide d(CGCAATTGCG)2 deduced from high-resolution 1H NMR Studies. Biochemistry. 1988 Jan 12;27(1):445–455. doi: 10.1021/bi00401a066. [DOI] [PubMed] [Google Scholar]
  9. Lown J. W., Krowicki K., Bhat U. G., Skorobogaty A., Ward B., Dabrowiak J. C. Molecular recognition between oligopeptides and nucleic acids: novel imidazole-containing oligopeptides related to netropsin that exhibit altered DNA sequence specificity. Biochemistry. 1986 Nov 18;25(23):7408–7416. doi: 10.1021/bi00371a024. [DOI] [PubMed] [Google Scholar]
  10. Pelton J. G., Wemmer D. E. Structural characterization of a 2:1 distamycin A.d(CGCAAATTGGC) complex by two-dimensional NMR. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5723–5727. doi: 10.1073/pnas.86.15.5723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pelton J. G., Wemmer D. E. Structural modeling of the distamycin A-d(CGCGAATTCGCG)2 complex using 2D NMR and molecular mechanics. Biochemistry. 1988 Oct 18;27(21):8088–8096. doi: 10.1021/bi00421a018. [DOI] [PubMed] [Google Scholar]
  12. Schultz P. G., Dervan P. B. Distamycin and penta-N-methylpyrrolecarboxamide binding sites on native DNA. A comparison of methidiumpropyl-EDTA-Fe(II) footprinting and DNA affinity cleaving. J Biomol Struct Dyn. 1984 Mar;1(5):1133–1147. doi: 10.1080/07391102.1984.10507508. [DOI] [PubMed] [Google Scholar]
  13. Schultz P. G., Dervan P. B. Sequence-specific double-strand cleavage of DNA by penta-N-methylpyrrolecarboxamide-EDTA X Fe(II). Proc Natl Acad Sci U S A. 1983 Nov;80(22):6834–6837. doi: 10.1073/pnas.80.22.6834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sklenár V., Brooks B. R., Zon G., Bax A. Absorption mode two-dimensional NOE spectroscopy of exchangeable protons in oligonucleotides. FEBS Lett. 1987 Jun 1;216(2):249–252. doi: 10.1016/0014-5793(87)80699-3. [DOI] [PubMed] [Google Scholar]
  15. Warshaw M. M., Cantor C. R. Oligonucleotide interactions. IV. Conformational differences between deoxy- and ribodinucleoside phosphates. Biopolymers. 1970;9(9):1079–1103. doi: 10.1002/bip.1970.360090910. [DOI] [PubMed] [Google Scholar]
  16. Yoon C., Privé G. G., Goodsell D. S., Dickerson R. E. Structure of an alternating-B DNA helix and its relationship to A-tract DNA. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6332–6336. doi: 10.1073/pnas.85.17.6332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Youngquist R. S., Dervan P. B. Sequence-specific recognition of B-DNA by oligo(N-methylpyrrolecarboxamide)s. Proc Natl Acad Sci U S A. 1985 May;82(9):2565–2569. doi: 10.1073/pnas.82.9.2565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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 Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES