EDD, a novel phosphotransferase domain common to mannose transporter EIIA, dihydroxyacetone kinase, and DegV

Abstract

Using a recently developed program (SCOPmap) designed to automatically assign new protein structures to existing evolutionary‐based classification schemes, we identify a evolutionarily conserved domain (EDD) common to three different folds: mannose transporter E IIA domain (EIIA‐man), d ihydroxyacetone kinase (Dak), and D egV. Several lines of evidence support unification of these three folds into a single superfamily: statistically significant sequence similarity detected by PSI‐BLAST; “closed structural grouping” using DALI Z‐scores (each protein inside a group finds all other group members with scores higher than those to proteins outside the group) that includes only these proteins sharing a unique α‐helical hairpin at the C‐terminus and excludes all other proteins with similar topology; similar domain fusions connect Dak and DegV, and genomic neighborhood organizations connect Dak and EIIA‐man. Finally, both Dak and EIIA‐man perform similar phosphotransfer reactions, suggesting a phosphotransferase activity for the DegV‐like family of proteins, whose function other than lipid binding revealed in the crystal structure remains unknown.