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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 1.0 ns 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.

Original languageEnglish
Pages (from-to)149-158
Number of pages10
JournalComputational Biology and Chemistry
Volume32
Issue number3
DOIs
Publication statusPublished - 2008 Jun 1
Externally publishedYes

Keywords

  • Molecular dynamics
  • Protein-DNA binding
  • Water-mediated interactions

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Organic Chemistry
  • Computational Mathematics

Fingerprint Dive into the research topics of 'Water-mediated interactions in the CRP-cAMP-DNA complex: Does water mediate sequence-specific binding at the DNA primary-kink site?'. Together they form a unique fingerprint.

  • Cite this