Kielkopf, Clara L. and Bremer, Ryan M. and White, Sarah and Szewczyk, Jason W. and Turner, James M. and Baird, Eldon E. and Dervan, Peter B. and Rees, Douglas C. (2000) Structural Effects of DNA Sequence on T•A Recognition by Hydroxypyrrole/Pyrrole Pairs in the Minor Groove. Journal of Molecular Biology, 295 (3). pp. 557-567. ISSN 0022-2836. http://resolver.caltech.edu/CaltechAUTHORS:20150108-155336917
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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.
| Item Type: | Article | |||||||||
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| Contact Email Address: | phoebe@caltech.edu | |||||||||
| 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. | |||||||||
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| Subject Keywords: | polyamides; hydroxypyrrole; sequence-specific recognition; nucleic acids; crystal-structure | |||||||||
| Record Number: | CaltechAUTHORS:20150108-155336917 | |||||||||
| Persistent URL: | http://resolver.caltech.edu/CaltechAUTHORS:20150108-155336917 | |||||||||
| Official Citation: | Clara L Kielkopf, Ryan E Bremer, Sarah White, Jason W Szewczyk, James M Turner, Eldon E Baird, Peter B Dervan, Douglas C Rees, Structural effects of DNA sequence on T·A recognition by hydroxypyrrole/pyrrole pairs in the minor groove, Journal of Molecular Biology, Volume 295, Issue 3, 21 January 2000, Pages 557-567, ISSN 0022-2836, http://dx.doi.org/10.1006/jmbi.1999.3364. (http://www.sciencedirect.com/science/article/pii/S0022283699933648) | |||||||||
| Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | |||||||||
| ID Code: | 53419 | |||||||||
| Collection: | CaltechAUTHORS | |||||||||
| Deposited By: | SWORD User | |||||||||
| Deposited On: | 14 Jan 2015 07:22 | |||||||||
| Last Modified: | 14 Jan 2015 07:22 |
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