Structural effects of DNA sequence on T.A recognition by hydroxypyrrole/pyrrole pairs in the minor groove.
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 A, 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.
Kielkopf
C L
CL
Division of Chemistry, California Institute of Technology, Pasadena, CA, 91125, USA.
Bremer
R E
RE
White
S
S
Szewczyk
J W
JW
Turner
J M
JM
Baird
E E
EE
Dervan
P B
PB
Rees
D C
DC
D000225:Adenine / Q000737:chemistry; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry
D009757:Nylons; D011758:Pyrroles; D004247:DNA; D000225:Adenine; D013941:Thymine