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

1ON8 の概要

• エントリーDOI: 10.2210/pdb1on8/pdb
• 関連するPDBエントリー: 1OMX 1OMZ 1ON6
• 分子名称: Alpha-1,4-N-acetylhexosaminyltransferase EXTL2, beta-D-glucopyranuronic acid-(1-3)-beta-D-galactopyranose, MANGANESE (II) ION, ... (6 entities in total)
• 機能のキーワード: rossmann fold, dxd motif, transferase
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Endoplasmic reticulum membrane ; Single-pass type II membrane protein : Q9ES89
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68547.52

構造登録者

Pedersen, L.C.,Dong, J.,Taniguchi, F.,Kitagawa, H.,Krahn, J.M.,Pedersen, L.G.,Sugahara, K.,Negishi, M. (登録日: 2003-02-27, 公開日: 2003-04-22, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.7 Å)