Institute of Chemistry, Academia Sinica* Institute of Biological Chemistry, Academia Sinica** Department of Chemical Engineering, Minghsin University of Science and Technology***
○Chin-Yu Chen* Tzu-Ping Ko** Chi-Rung Lee*** Andrew H.-J. Wang**
Recent surveys of high-resolution protein-DNA crystal structures have noted that solvent molecules are commonly present within the protein-DNA interfaces. Indeed, water-mediated interactions can be as common as direct H-bonds or salt links. Putting these results together has revealed that protein-DNA complexes are quite diverse in their use of water. In the non-sequence specific DNA binding proteins, interfacial water molecules may act as “modulators” for their binding to DNA of varying sequence without adding specificities. When sequence specific DNA binding proteins bound to non-cognate DNA, more waters remained at the interface of the complexes. These waters may behave as a kind of molecular glue allowing the protein to scan along the DNA for their specific binding sites. In different protein-DNA complexes, we also find that proteins switch their specificity, i.e., conversion of a nonspecific to a specific complex by replacing using water-mediated hydrogen bond interactions with direct hydrogen bond contacts. In many others, however, two to four water molecules remain at the interface and these play an important role in the specificity of recognition, in some cases facilitating a fluctuating network of hydrogen bonds between the sequence specific protein and DNA. Since DNA hydration patterns are sequence dependent, proteins recognize the DNA hydration structures rather than DNA sequence upon forming the complexes.