...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochimica et biophysica acta: BBA: International journal of biochemistry, biophysics and molecular biololgy. Proteins and Proteomics >Structure and function of a highly active Bile Salt Hydrolase (BSH) from Enterococcus faecalis and post-translational processing of BSH enzymes
【24h】

Structure and function of a highly active Bile Salt Hydrolase (BSH) from Enterococcus faecalis and post-translational processing of BSH enzymes

机译：来自肠球菌的高活性胆汁盐水解酶（BSH）的结构和功能来自肠球菌粪便和BSH酶的翻译后加工

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Bile Salt Hydrolase (BSH), a member of Cholylglycine hydrolase family, catalyzes the de-conjugation of bile acids and is evolutionarily related to penicillin V acylase (PVA) that hydrolyses a different substrate such as penicillin V. We report the three-dimensional structure of a BSH enzyme from the Gram-positive bacteria Enterococcus faecalis (EfBSH) which has manifold higher hydrolase activity compared to other known BSHs and displays unique allosteric catalytic property. The structural analysis revealed reduced secondary structure content compared to other known BSH structures, particularly devoid of an anti-parallel beta-sheet in the assembly loop and part of a beta-strand is converted to increase the length of a substrate binding loop 2. The analysis of the substrate binding pocket showed reduced volume owing to altered loop conformations and increased hydrophobicity contributed by a higher ratio of hydrophobic to hydrophilic groups present. The aromatic residues F18, Y20 and F65 participate in substrate binding. Thus, their mutation affects enzyme activity. Docking and Molecular Dynamics simulation studies showed effective polar complementarity present for the three hydroxyl (-OH) groups of GCA substrate in the binding site contributing to higher substrate specificity and efficient catalysis. These are unique features characteristics of this BSH enzyme and thought to contribute to its higher activity and specificity towards bile salts as well as allosteric effects. Further, mechanism of autocatalytic processing of Cholylglycine Hydrolases by the excision of an N-terminal Pre-peptide was examined by inserting different N-terminal pre-peptides in EfBSH sequence. The results suggest that two serine residues next to nucleophile cysteine are essential for autocalytic processing to remove precursor peptide. Since pre-peptide is absent in EfBSH the mutation of these serines is tolerated. This suggests that an evolution-mediated subordination of the pre-peptide excision site resulted in loss of pre-peptide in EfBSH and other related Cholylglycine hydrolases.
机译：胆汁盐水解酶（BSH），胆甘氨酸水解酶系列的成员，催化胆汁酸的去缀合，与青霉素V酰基化酶（PVA）进行进化，其水解不同的基材，例如青霉素V.我们报告了三维结构来自革兰氏阳性细菌肠球菌（EFBSH）的BSH酶，与其他已知的BSH相比具有歧管较高的水解酶活性，并显示出独特的变构催化性能。与其他已知的BSH结构相比，结构分析显示出减少的二次结构含量，特别是在组装环中的抗平行β-片，并转换β股的一部分以增加基板结合环2的长度。由于改变的环构象，并且由于存在改变的环形构象和增加的疏水性而导致的疏水性增加，疏水性增加的疏水性增加的分析。芳族残基F18，Y20和F65参与底物结合。因此，它们的突变影响酶活性。对接和分子动力学模拟研究表明，在有助于更高的底物特异性和有效催化的结合位点中，GCA底物的三个羟基（-OH）基团的有效极性互补性。这些是这种BSH酶的独特特征，并且据思想为其更高的活性和对胆汁盐的特异性以及血糖效应有助于。此外，通过在EFBSH序列中插入不同的N-末端预肽来检查通过切除N-末端预肽的胆甘氨酸水解酶的自催化处理的机制。结果表明，亲核性半胱氨酸旁边的两个丝氨酸残基对于去除前体肽来说是必不可少的自粒子加工。由于在EFBSH中不存在预肽，因此耐受这些丝氨酸的突变。这表明对肽预切除遗传学遗址的进化介导的从属导致EFBSH和其他相关胆糖水解酶中的预肽的损失。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号