Water-mediated interactions in the CRP-cAMP-DNA complex: Does water mediate sequence-specific binding at the DNA primary-kink site?

  • Authors:

  • Bryan M. B. VanSchouwen;Heather L. Gordon;Stuart M. Rothstein;Yuto Komeiji;Kaori Fukuzawa;Shigenori Tanaka

  • Affiliations:

  • Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada;Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada;Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada;Japan Science and Technology Agency, CREST, Japan and National Institute of Advanced Industrial Science and Technology, AIST, Central 2, Tsukuba 305-8568, Japan;Japan Science and Technology Agency, CREST, Japan and Mizuho Information & Research Institute, Inc., 2-3 Kanda Nishiki-cho, Chiyoda-ku, Tokyo 101-8443, Japan;Japan Science and Technology Agency, CREST, Japan and Graduate School of Human Development and Environment, Kobe University, 3-11, Tsurukabuto, Nada, Kobe 657-8501, Japan

  • Venue:
  • Computational Biology and Chemistry
  • Year:
  • 2008

Quantified Score

Hi-index 0.00

Visualization

Abstract

The cyclic AMP receptor protein (CRP) of Escherichia coli binds preferentially to DNA sequences possessing a T:A base pair at position 6 (at which the DNA becomes kinked), but with which it does not form any direct interactions. It has been proposed that indirect readout is involved in CRP-DNA binding, in which specificity for this base pair is primarily related to sequence effects on the energetic susceptibility of the DNA to kink formation. In the current study, the possibility of contributions to indirect readout by water-mediated hydrogen bonding of CRP with the T:A base pair was investigated. A 1.0ns molecular dynamics simulation of the CRP-cAMP-DNA complex in explicit solvent was performed, and assessed for water-mediated CRP-DNA hydrogen bonds; results were compared to several X-ray crystal structures of comparable complexes. While several water-mediated CRP-DNA hydrogen bonds were identified, none of these involved the T:A base pair at position 6. Therefore, the sequence specificity for this base pair is not likely enhanced by water-mediated hydrogen bonding with the CRP.