The homeobox domain was first identified in a number of drosophila homeotic and segmentation proteins, but is now known to be well-conserved in many other animals, including vertebrates [<cite idref="PUB00000591"/>, <cite idref="PUB00005390"/>, <cite idref="PUB00005540"/>]. Hox genes encode homeodomain-containing transcriptional regulators that operate differential genetic programs along the anterior-posterior axis of animal bodies [<cite idref="PUB00010002"/>]. The domain binds DNA through a helix-turn-helix (HTH) structure. The HTH motif is characterised by two alpha-helices, which make intimate contacts with the DNA and are joined by a short turn. The second helix binds to DNA via a number of hydrogen bonds and hydrophobic interactions, which occur between specific side chains and the exposed bases and thymine methyl groups within the major groove of the DNA [<cite idref="PUB00005540"/>]. The first helix helps to stabilise the structure. <p>The motif is very similar in sequence and structure in a wide range of DNA-binding proteins (e.g., cro and repressor proteins, homeotic proteins, etc.). One of the principal differences between HTH motifs in these different proteins arises from the stereo-chemical requirement for glycine in the turn which is needed to avoid steric interference of the beta-carbon with the main chain: for cro and repressor proteins the glycine appears to be mandatory, while for many of the homeotic and other DNA-binding proteins the requirement is relaxed.</p> Homeobox, conserved site