1FGG

CRYSTAL STRUCTURE OF 1,3-GLUCURONYLTRANSFERASE I (GLCAT-I) COMPLEXED WITH GAL-GAL-XYL, UDP, AND MN2+

Summary for 1FGG

• Entry DOI: 10.2210/pdb1fgg/pdb
• Descriptor: GLUCURONYLTRANSFERASE I, beta-D-galactopyranose-(1-3)-beta-D-galactopyranose, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: glucuronyltransferase, udp, ddd, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Golgi apparatus membrane ; Single-pass type II membrane protein : O94766
• Total number of polymer chains: 2
• Total formula weight: 59244.62

Authors

Pedersen, L.C.,Tsuchida, K.,Kitagawa, H.,Sugahara, K.,Darden, T.A. (deposition date: 2000-07-28, release date: 2001-01-31, Last modification date: 2024-03-13)

Primary citation

Pedersen, L.C.,Tsuchida, K.,Kitagawa, H.,Sugahara, K.,Darden, T.A.,Negishi, M.
Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I.
J.Biol.Chem., 275:34580-34585, 2000

PubMed Abstract: Human beta1,3-glucuronyltransferase I (GlcAT-I) is a central enzyme in the initial steps of proteoglycan synthesis. GlcAT-I transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal beta 1-3Gal beta 1-4Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. We have now determined the crystal structure of GlcAT-1 at 2.3 A in the presence of the donor substrate product UDP, the catalytic Mn(2+) ion, and the acceptor substrate analog Gal beta 1-3Gal beta 1-4Xyl. The enzyme is a alpha/beta protein with two subdomains that constitute the donor and acceptor substrate binding site. The active site residues lie in a cleft extending across both subdomains in which the trisaccharide molecule is oriented perpendicular to the UDP. Residues Glu(227), Asp(252), and Glu(281) dictate the binding orientation of the terminal Gal-2 moiety. Residue Glu(281) is in position to function as a catalytic base by deprotonating the incoming 3-hydroxyl group of the acceptor. The conserved DXD motif (Asp(194), Asp(195), Asp(196)) has direct interaction with the ribose of the UDP molecule as well as with the Mn(2+) ion. The key residues involved in substrate binding and catalysis are conserved in the glucuronyltransferase family as well as other glycosyltransferases.

PubMed: 10946001
DOI: 10.1074/jbc.M007399200

Experimental method

X-RAY DIFFRACTION (2.3 Å)