| First Author | Holm L | Year | 1995 |
| Journal | EMBO J | Volume | 14 |
| Issue | 7 | Pages | 1287-93 |
| PubMed ID | 7729407 | Mgi Jnum | J:24501 |
| Mgi Id | MGI:72240 | Doi | 10.1002/j.1460-2075.1995.tb07114.x |
| Citation | Holm L, et al. (1995) Evolutionary link between glycogen phosphorylase and a DNA modifying enzyme. EMBO J 14(7):1287-93 |
| abstractText | 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. |
