Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme.
We report here an unexpected similarity in three-dimensional structure between glucosyltransferases involved in 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 is the metabolic enzyme glycogen phosphorylase, alias 1.4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase. Structural alignment revealed that the entire structure of beta-glucosyltransferase is topographically equivalent to the catalytic core of the much larger glycogen phosphorylase. The match includes two domains in similar relative orientation and connecting helices, with a positional root-mean-square deviation of only 3.4 A for 256 C alpha atoms. An interdomain rotation seen in the R- to T-state transition of glycogen phosphorylase is similar to that observed in beta-glucosyltransferase on substrate binding. Although not a single functional residue is identical, there are striking similarities in the spatial arrangement and in the chemical nature of the substrates. The functional analogies are (beta-glucosyltransferase-glycogen phosphorylase): ribose ring of UDP-pyridoxal ring of pyridoxal phosphate co-enzyme; phosphates of UDP-phosphate of co-enzyme and reactive orthophosphate; glucose unit transferred to DNA-terminal glucose unit extracted from glycogen. We anticipate the discovery of additional structurally conserved members of the emerging glucosyltransferase superfamily derived from a common ancient evolutionary ancestor of the two enzymes.
Holm
L
L
EMBL, Heidelberg, Germany.
Sander
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017122:Bacteriophage T4 / Q000201:enzymology; D001665:Binding Sites; D005075:Biological Evolution; D017124:Conserved Sequence; D005964:Glucosyltransferases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D006005:Phosphorylases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017433:Protein Structure, Secondary; D011817:Rabbits; D017386:Sequence Homology, Amino Acid
D005964:Glucosyltransferases; D006005:Phosphorylases; C026585:DNA beta-glucosyltransferase