Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V

• DOI: 10.1038/s41467-018-05931-w
• Publication Date: 2018-08-17T10:59:30Z
• Authors: Masamichi Nagae; Yasuhiko Kizuka; Emiko Mihara; Yu Kitago; Shinya Hanashima; Yukishige Ito; Junichi Takagi; Naoyuki Taniguchi; Yoshiki Yamaguchi
• Keywords: Branching (polymer chemistry); Acceptor

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