5ZIC

Crystal structure of human GnT-V luminal domain in complex with acceptor sugar

5ZIC の概要

• エントリーDOI: 10.2210/pdb5zic/pdb
• 関連するPDBエントリー: 5ZIB
• 分子名称: Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-6-thio-alpha-D-mannopyranose-(1-6)-beta-D-mannopyranose (3 entities in total)
• 機能のキーワード: glycosyltransferase cancer metastasis luminal protein, sugar binding protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 120720.71

構造登録者

Nagae, M.,Yamaguchi, Y. (登録日: 2018-03-14, 公開日: 2018-08-01, 最終更新日: 2023-11-22)

主引用文献

Nagae, M.,Kizuka, Y.,Mihara, E.,Kitago, Y.,Hanashima, S.,Ito, Y.,Takagi, J.,Taniguchi, N.,Yamaguchi, Y.
Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V.
Nat Commun, 9:3380-3380, 2018

PubMed Abstract: N-acetylglucosaminyltransferase-V (GnT-V) alters the structure of specific N-glycans by modifying α1-6-linked mannose with a β1-6-linked N-acetylglucosamine branch. β1-6 branch formation on cell surface receptors accelerates cancer metastasis, making GnT-V a promising target for drug development. However, the molecular basis of GnT-V's catalytic mechanism and substrate specificity are not fully understood. Here, we report crystal structures of human GnT-V luminal domain with a substrate analog. GnT-V luminal domain is composed of a GT-B fold and two accessary domains. Interestingly, two aromatic rings sandwich the α1-6 branch of the acceptor N-glycan and restrain the global conformation, partly explaining the fine branch specificity of GnT-V. In addition, interaction of the substrate N-glycoprotein with GnT-V likely contributes to protein-selective and site-specific glycan modification. In summary, the acceptor-GnT-V complex structure suggests a catalytic mechanism, explains the previously observed inhibition of GnT-V by branching enzyme GnT-III, and provides a basis for the rational design of drugs targeting N-glycan branching.

PubMed: 30140003
DOI: 10.1038/s41467-018-05931-w

実験手法

X-RAY DIFFRACTION (2.1 Å)