Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme.

摘要: We report here an unexpected similarity in three-dimensional structure between glucosyltransferases involved very different biochemical pathways, with interesting evolutionary and functional implications. One is the DNA modifying enzyme beta-glucosyltransferase from bacteriophage T4, alias UDP-glucose:5-hydroxymethyl-cytosine beta-glucosyltransferase. The other metabolic glycogen phosphorylase, 1.4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase. Structural alignment revealed that entire of topographically equivalent to catalytic core much larger phosphorylase. match includes two domains similar relative orientation connecting helices, a positional root-mean-square deviation only 3.4 A for 256 C alpha atoms. An interdomain rotation seen R- T-state transition phosphorylase observed on substrate binding. Although not single residue identical, there are striking similarities spatial arrangement chemical nature substrates. analogies (beta-glucosyltransferase-glycogen phosphorylase): ribose ring UDP-pyridoxal pyridoxal phosphate co-enzyme; phosphates UDP-phosphate co-enzyme reactive orthophosphate; glucose unit transferred DNA-terminal extracted glycogen. anticipate discovery additional structurally conserved members emerging glucosyltransferase superfamily derived common ancient ancestor enzymes.