Gene encoding aspartyl dipeptidase from Xenopus levies (PepExl) is upregulated by thyroid hormone and is proposed to play a significant role in resorption of tadpole tail during metamorphosis. However, the importance of peptidase activity for the resorption of the tail remain elusive. Here we report the crystal structures of first eukaryotic S51 peptidase, PepExl, in its ligand-free and Asp-bound states at 1.4 and 1.8 Ã… resolutions, respectively. The active site is located at dimeric interface and the catalytic triad is found to be dissembled in ligand-free and assembled in Asp-bound state. Structural comparison and molecular dynamic simulations of ligand-free and Asp-bound states shows that distinct loop (loop-A) plays an important role in active site shielding, substrate binding and enzyme activation. This study illuminates the Asp-X dipeptide binding in PepExl is associated with ordering of the loop-A and assembly of residues of catalytic triad in active conformation for enzymatic activity.

中文翻译：

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非洲爪蟾天冬氨酰二肽酶的晶体结构揭示了配体结合诱导的环排序和催化三联体组装

来自非洲爪蟾的编码天冬氨酰二肽酶的基因(PepExl) 被甲状腺激素上调，并被认为在变态过程中蝌蚪尾巴的再吸收中起重要作用。然而，肽酶活性对尾部吸收的重要性仍然难以捉摸。在这里我们报告第一个真核S51 肽酶，PepExl，在其无配体和Asp 绑定状态分别在1.4 和1.8 × 分辨率的晶体结构。活性位点位于二聚体界面，发现催化三联体以无配体的形式分散并以 Asp 结合状态组装。无配体和 Asp 结合状态的结构比较和分子动力学模拟表明，不同的环 (loop-A) 在活性位点屏蔽、底物结合和酶激活中起重要作用。