5FV9

Crystal structure of GalNAc-T2 in complex with compound 16d

5FV9 の概要

• エントリーDOI: 10.2210/pdb5fv9/pdb
• 分子名称: GALNAC-T2, URIDINE-5'-DIPHOSPHATE, MANGANESE (II) ION, ... (7 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Golgi apparatus, Golgi stack membrane ; Single-pass type II membrane protein : Q10471
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 394569.44

構造登録者

Ghirardello, M.,Rivas, M.,Lacetera, A.,Delso, I.,Lira-Navarrete, E.,Tejero, T.,Martin-Santamaria, S.,Hurtado-Guerrero, R.,Merino, P. (登録日: 2016-02-03, 公開日: 2016-03-09, 最終更新日: 2024-10-23)

主引用文献

Ghirardello, M.,De Las Rivas, M.,Lacetera, A.,Delso, I.,Lira-Navarrete, E.,Tejero, T.,Martin-Santamaria, S.,Hurtado-Guerrero, R.,Merino, P.
Glycomimetics Targeting Glycosyltransferases: Synthetic, Computational and Structural Studies of Less-Polar Conjugates.
Chemistry, 22:7215-, 2016

PubMed Abstract: The Leloir donors are nucleotide sugars essential for a variety of glycosyltransferases (GTs) involved in the transfer of a carbohydrate to an acceptor substrate, typically a protein or an oligosaccharide. A series of less-polar nucleotide sugar analogues derived from uridine have been prepared by replacing one phosphate unit with an alkyl chain. The methodology is based on the radical hydrophosphonylation of alkenes, which allows coupling of allyl glycosyl compounds with a phosphate unit suitable for conjugation to uridine. Two of these compounds, the GalNAc and galactose derivatives, were further tested on a model GT, such as GalNAc-T2 (an important GT widely distributed in human tissues), to probe that both compounds bound in the medium-high micromolar range. The crystal structure of GalNAc-T2 with the galactose derivative traps the enzyme in an inactive form; this suggests that compounds only containing the β-phosphate could be efficient ligands for the enzyme. Computational studies with GalNAc-T2 corroborate these findings and provide further insights into the mechanism of the catalytic cycle of this family of enzymes.

PubMed: 27071848
DOI: 10.1002/CHEM.201600467

実験手法

X-RAY DIFFRACTION (2.07 Å)