EDD, a novel phosphotransferase domain common to mannose transporter EIIA, dihydroxyacetone kinase, and DegV.
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 EIIA domain (EIIA-man), dihydroxyacetone kinase (Dak), and DegV. 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 alpha-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.
Kinch
Lisa N
LN
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9050, USA.
Cheek
Sara
S
Grishin
Nick V
NV
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D029968:Escherichia coli Proteins; D019143:Evolution, Molecular; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008358:Mannose / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000737:chemistry*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D008055:Lipids; C032242:crr protein, E coli; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D017853:Phosphotransferases (Alcohol Group Acceptor); C023132:glycerone kinase; D008358:Mannose