5ZIB

Crystal structure of human GnT-V luminal domain in apo form

Summary for 5ZIB

• Entry DOI: 10.2210/pdb5zib/pdb
• Related: 5ZIC
• Descriptor: Alpha-1,6-mannosylglycoprotein 6-beta-N-acetylglucosaminyltransferase A, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: glycosyltransferase cancer metastasis luminal protein, sugar binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 71807.45

Authors

Nagae, M.,Yamaguchi, Y. (deposition date: 2018-03-14, release date: 2018-08-01, Last modification date: 2024-10-09)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)