Insights into activity and inhibition from the crystal structure of human O-GlcNAcase
Insights into activity and inhibition from the crystal structure of human O-GlcNAcase
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DOI：
10.1038/nchembio.2357
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发表时间：
2017-06-01
影响因子：
14.8
通讯作者：
Klein, Daniel J.
中科院分区：
文献类型：
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作者：
Elsen, Nathaniel L.;Patel, Sangita B.;Klein, Daniel J.
O-GlcNAc水解酶（OGA）催化从丝氨酸和苏氨酸残基去除β-连接的N-乙酰基-D-葡糖胺。我们报告晶体结构的智人OGA催化结构域在载脂蛋白和抑制状态，揭示了灵活的二聚体，显示三个独特的构象，其特征在于由子域α-螺旋交换。这些结果确定了新的结构特征的底物结合槽附近的催化位点，并打开了新的机会，结构，机制和药物发现活动。
O-GlcNAc hydrolase (OGA) catalyzes removal of beta-linked N-acetyl-D-glucosamine from serine and threonine residues. We report crystal structures of Homo sapiens OGA catalytic domain in apo and inhibited states, revealing a flexible dimer that displays three unique conformations and is characterized by subdomain alpha-helix swapping. These results identify new structural features of the substrate-binding groove adjacent to the catalytic site and open new opportunities for structural, mechanistic and drug discovery activities.