1ON8

Crystal structure of mouse alpha-1,4-N-acetylhexosaminyltransferase (EXTL2) with UDP and GlcUAb(1-3)Galb(1-O)-naphthalenelmethanol an acceptor substrate analog

Summary for 1ON8

• Entry DOI: 10.2210/pdb1on8/pdb
• Related: 1OMX 1OMZ 1ON6
• Descriptor: Alpha-1,4-N-acetylhexosaminyltransferase EXTL2, beta-D-glucopyranuronic acid-(1-3)-beta-D-galactopyranose, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: rossmann fold, dxd motif, transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : Q9ES89
• Total number of polymer chains: 2
• Total formula weight: 68547.52

Authors

Pedersen, L.C.,Dong, J.,Taniguchi, F.,Kitagawa, H.,Krahn, J.M.,Pedersen, L.G.,Sugahara, K.,Negishi, M. (deposition date: 2003-02-27, release date: 2003-04-22, Last modification date: 2024-11-20)

Primary citation

Pedersen, L.C.,Dong, J.,Taniguchi, F.,Kitagawa, H.,Krahn, J.M.,Pedersen, L.G.,Sugahara, K.,Negishi, M.
Crystal structure of an alpha-1,4-N-acetylhexosaminyltransferase (EXTL2), a member of the exostosin gene family involved in heparan sulfate biosynthesis
J.Biol.Chem., 278:14420-14428, 2003

PubMed Abstract: EXTL2, an alpha1,4-N-acetylhexosaminyltransferase, catalyzes the transfer reaction of N-acetylglucosamine and N-acetylgalactosamine from the respective UDP-sugars to the non-reducing end of [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol, an acceptor substrate analog of the natural common linker of various glycosylaminoglycans. We have solved the x-ray crystal structure of the catalytic domain of mouse EXTL2 in the apo-form and with donor substrates UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine. In addition, a structure of the ternary complex with UDP and the acceptor substrate analog [glucuronic acid]beta1-3[galactose]beta1-O-naphthalenemethanol has been determined. These structures reveal three highly conserved residues, Asn-243, Asp-246, and Arg-293, located at the active site. Mutation of these residues greatly decreases the activity. In the ternary complex, an interaction exists between the beta-phosphate of the UDP leaving group and the acceptor hydroxyl of the substrate that may play a functional role in catalysis. These structures represent the first structures from the exostosin gene family and provide important insight into the mechanisms of alpha1,4-N-acetylhexosaminyl transfer in heparan biosynthesis.

PubMed: 12562774
DOI: 10.1074/jbc.M210532200

Experimental method

X-RAY DIFFRACTION (2.7 Å)