Control of DNA minor groove width and Fis protein binding by the purine 2-amino group

Nucleic Acids Res. 2013 Jul;41(13):6750-60. doi: 10.1093/nar/gkt357. Epub 2013 May 9.


The width of the DNA minor groove varies with sequence and can be a major determinant of DNA shape recognition by proteins. For example, the minor groove within the center of the Fis-DNA complex narrows to about half the mean minor groove width of canonical B-form DNA to fit onto the protein surface. G/C base pairs within this segment, which is not contacted by the Fis protein, reduce binding affinities up to 2000-fold over A/T-rich sequences. We show here through multiple X-ray structures and binding properties of Fis-DNA complexes containing base analogs that the 2-amino group on guanine is the primary molecular determinant controlling minor groove widths. Molecular dynamics simulations of free-DNA targets with canonical and modified bases further demonstrate that sequence-dependent narrowing of minor groove widths is modulated almost entirely by the presence of purine 2-amino groups. We also provide evidence that protein-mediated phosphate neutralization facilitates minor groove compression and is particularly important for binding to non-optimally shaped DNA duplexes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Base Pairing
  • DNA / chemistry*
  • DNA / metabolism
  • Factor For Inversion Stimulation Protein / chemistry*
  • Factor For Inversion Stimulation Protein / metabolism
  • Molecular Dynamics Simulation
  • Nucleic Acid Conformation
  • Phosphates / chemistry
  • Protein Binding
  • Purines / chemistry


  • Factor For Inversion Stimulation Protein
  • Phosphates
  • Purines
  • DNA