2018年12月
Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V
Nature Communications
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- 巻
- 9
- 号
- 1
- 開始ページ
- 3380
- 終了ページ
- 3380
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41467-018-05931-w
- 出版者・発行元
- Springer Science and Business Media {LLC}
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.
- リンク情報
- ID情報
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- DOI : 10.1038/s41467-018-05931-w
- ORCIDのPut Code : 47493675
- PubMed ID : 30140003
- PubMed Central 記事ID : PMC6107550