1fgg
From Proteopedia
CRYSTAL STRUCTURE OF 1,3-GLUCURONYLTRANSFERASE I (GLCAT-I) COMPLEXED WITH GAL-GAL-XYL, UDP, AND MN2+
Structural highlights
Disease[B3GA3_HUMAN] Defects in B3GAT3 are the cause of multiple joint dislocations short stature craniofacial dysmorphism and congenital heart defects (JDSSDHD) [MIM:245600]. An autosomal recessive disease characterized by dysmorphic facies, bilateral dislocations of the elbows, hips, and knees, clubfeet, and short stature, as well as cardiovascular defects.[1] Function[B3GA3_HUMAN] Glycosaminoglycans biosynthesis. Involved in forming the linkage tetrasaccharide present in heparan sulfate and chondroitin sulfate. Transfers a glucuronic acid moiety from the uridine diphosphate-glucuronic acid (UDP-GlcUA) to the common linkage region trisaccharide Gal-beta-1,3-Gal-beta-1,4-Xyl covalently bound to a Ser residue at the glycosaminylglycan attachment site of proteoglycans. Can also play a role in the biosynthesis of l2/HNK-1 carbohydrate epitope on glycoproteins. Shows strict specificity for Gal-beta-1,3-Gal-beta-1,4-Xyl, exhibiting negligible incorporation into other galactoside substrates including Galbeta1-3Gal beta1-O-benzyl, Galbeta1-4GlcNAc and Galbeta1-4Glc. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman 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. Heparan/chondroitin sulfate biosynthesis. Structure and mechanism of human glucuronyltransferase I.,Pedersen LC, Tsuchida K, Kitagawa H, Sugahara K, Darden TA, Negishi M J Biol Chem. 2000 Nov 3;275(44):34580-5. PMID:10946001[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Darden, T A | Kitagawa, H | Pedersen, L C | Sugahara, K | Tsuchida, K | Ddd | Glucuronyltransferase | Transferase | Udp
