Presence of pKa Perturbations Among Homeodomain Residues Facilitates DNA Binding.

Homeodomain containing proteins are a broad class of DNA binding proteins that are believed to primarily function as transcription factors. Electrostatics interactions have been demonstrated to be critical for the binding of the homeodomain to DNA. An examination of the electrostatic state of homeodomain residues involved in DNA phosphate binding has demonstrated the conserved presence of upward shifted pKa values among the basic residue of lysine and arginine. It is believed that these pKa perturbations work to facilitate binding to DNA since they ensure that the basic residues always retain a positive charge.