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

Presence of pKa Perturbations Among Homeodomain Residues Facilitates DNA Binding