Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA.
Article Details
- CitationCopy to clipboard
Pedersen LC, Darden TA, Negishi M
Crystal structure of beta 1,3-glucuronyltransferase I in complex with active donor substrate UDP-GlcUA.
J Biol Chem. 2002 Jun 14;277(24):21869-73. Epub 2002 Apr 11.
- PubMed ID
- 11950836 [ View in PubMed]
- Abstract
Beta1,3-glucuronyltransferase (GlcAT-I) is an essential enzyme involved in heparan sulfate and chondroitin sulfate biosynthesis. GlcAT-I is an inverting glycosyltransferase that catalyzes the transfer of glucuronic acid (GlcUA) to the common growing linker region Galbeta1-3Galbeta1-4Xyl that is attached to a serine side chain of a core protein. Previously the structure of GlcAT-I has been solved in the presence of the donor product UDP and an acceptor analog Galbeta1-3Galbeta1-4Xyl (Pedersen, L. C., Tsuchida, K., Kitagawa, H., Sugahara, K., Darden, T. A. & Negishi, M. (2000) J. Biol. Chem. 275, 34580-34585). Here we report the x-ray crystal structure of GlcAT-I in complex with the complete donor UDP-GlcUA, thereby providing structures of an inverting glycosyltransferase in which both the complete donor and acceptor substrates are present in the active site. This structure supports the in-line displacement reaction mechanism previously proposed. It also provides information on the essential amino acid residues that determine donor substrate specificity.