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Published January 21, 2000 | public
Journal Article

Structural Effects of DNA Sequence on T•A Recognition by Hydroxypyrrole/Pyrrole Pairs in the Minor Groove

Abstract

Synthetic polyamides composed of three types of aromatic amino acids, N-methylimidazole (Im), N-methylpyrrole (Py) and N-methyl-3-hydroxypyrrole (Hp) bind specific DNA sequences as antiparallel dimers in the minor groove. The side-by-side pairings of aromatic rings in the dimer afford a general recognition code that allows all four base-pairs to be distinguished. To examine the structural consequences of changing the DNA sequence context on T•A recognition by Hp/Py pairs in the minor groove, crystal structures of polyamide dimers (ImPyHpPy)_2 and the pyrrole counterpart (ImPyPyPy)_2 bound to the six base-pair target site 5′-AGATCT-3′ in a ten base-pair oligonucleotide have been determined to a resolution of 2.27 and 2.15 Å, respectively. The structures demonstrate that the principles of Hp/Py recognition of T•A are consistent between different sequence contexts. However, a general structural explanation for the non-additive reduction in binding affinity due to introduction of the hydroxyl group is less clear. Comparison with other polyamide-DNA cocrystal structures reveals structural themes and differences that may relate to sequence preference.

Additional Information

© 2000 Academic Press. Received 1 September 1999; received in revised form 30 October 1999; accepted 2 November 1999. We are grateful to the NIH for research support, to the NSF and NIH for predoctoral fellowships to C.L.K. and R.E.B., to J. Edward Richter for an undergraduate fellowship to J.M.T., and to the HHMI for a predoctoral fellowship to E.E.B. We thank A. Chirino and M. Williamson for assistance with computational and X-ray equipment, respectively, and S. Horvath for oligonucleotide synthesis.

Additional details

Created:
August 21, 2023
Modified:
October 19, 2023