TY - JOUR
T1 - Water-mediated interactions in the CRP-cAMP-DNA complex
T2 - Does water mediate sequence-specific binding at the DNA primary-kink site?
AU - VanSchouwen, Bryan M.B.
AU - Gordon, Heather L.
AU - Rothstein, Stuart M.
AU - Komeiji, Yuto
AU - Fukuzawa, Kaori
AU - Tanaka, Shigenori
PY - 2008/6/1
Y1 - 2008/6/1
N2 - 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.
AB - 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.
KW - Molecular dynamics
KW - Protein-DNA binding
KW - Water-mediated interactions
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U2 - 10.1016/j.compbiolchem.2008.01.001
DO - 10.1016/j.compbiolchem.2008.01.001
M3 - Article
C2 - 18356111
AN - SCOPUS:43249090774
VL - 32
SP - 149
EP - 158
JO - Computational Biology and Chemistry
JF - Computational Biology and Chemistry
SN - 1476-9271
IS - 3
ER -