4PXQ

Crystal structure of D-glucuronyl C5-epimerase in complex with heparin hexasaccharide

4PXQ の概要

• エントリーDOI: 10.2210/pdb4pxq/pdb
• 関連するPDBエントリー: 4PW2
• 分子名称: D-glucuronyl C5 epimerase B, 4-deoxy-2-O-sulfo-alpha-L-threo-hex-4-enopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose-(1-4)-2-O-sulfo-alpha-L-idopyranuronic acid-(1-4)-2-deoxy-6-O-sulfo-2-(sulfoamino)-alpha-D-glucopyranose (3 entities in total)
• 機能のキーワード: epimerization enzyme, multiple domain structure, heparan sulfate c5-epimerase, heparin, heparan sulfate, isomerase
• 由来する生物種: Danio rerio (leopard danio,zebra danio,zebra fish)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 135737.20

構造登録者

Ke, J.,Qin, Y.,Gu, X.,Tan, J.,Brunzelle, J.S.,Xu, H.E.,Ding, K. (登録日: 2014-03-24, 公開日: 2015-01-14, 最終更新日: 2024-02-28)

主引用文献

Qin, Y.,Ke, J.,Gu, X.,Fang, J.,Wang, W.,Cong, Q.,Li, J.,Tan, J.,Brunzelle, J.S.,Zhang, C.,Jiang, Y.,Melcher, K.,Li, J.P.,Xu, H.E.,Ding, K.
Structural and Functional Study of d-Glucuronyl C5-epimerase.
J.Biol.Chem., 290:4620-4630, 2015

PubMed Abstract: Heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. D-glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis, converting D-glucuronic acid to L-iduronic acid to increase HS flexibility. This modification of HS is important for protein ligand recognition. We have determined the crystal structures of Glce in apo-form (unliganded) and in complex with heparin hexasaccharide (product of Glce following O-sulfation), both in a stable dimer conformation. A Glce dimer contains two catalytic sites, each at a positively charged cleft in C-terminal α-helical domains binding one negatively charged hexasaccharide. Based on the structural and mutagenesis studies, three tyrosine residues, Tyr(468), Tyr(528), and Tyr(546), in the active site were found to be crucial for the enzymatic activity. The complex structure also reveals the mechanism of product inhibition (i.e. 2-O- and 6-O-sulfation of HS keeps the C5 carbon of L-iduronic acid away from the active-site tyrosine residues). Our structural and functional data advance understanding of the key modification in HS biosynthesis.

PubMed: 25568314
DOI: 10.1074/jbc.M114.602201

実験手法

X-RAY DIFFRACTION (2.2 Å)