...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Catalysis by the isolated tryptophan tryptophylquinone-containing subunit of aromatic amine dehydrogenase is distinct from native enzyme and synthetic model compounds and allows further probing of TTQ mechanismt
【24h】

Catalysis by the isolated tryptophan tryptophylquinone-containing subunit of aromatic amine dehydrogenase is distinct from native enzyme and synthetic model compounds and allows further probing of TTQ mechanismt

机译：芳香族胺脱氢酶的分离的含色氨酸色氨酸醌的亚基的催化作用不同于天然酶和合成模型化合物，并允许进一步探究TTQ机制

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

Para-substituted benzylamines are poor reactivity probes for structure-reactivity studies with TTQ-dependent aromatic amine dehydrogenase (AADH). In this study, we combine kinetic isotope effects (KIES) with structure-reactivity studies to show that para-substituted benzylamines are good reactivity probes of TTQ mechanism with the isolated TTQ-containing subunit of AADH. Contrary to the TTQ-containing subunit of methylamine dehydrogenase (MADH), which is catalytically inactive, the small subunit of AADH catalyzes the oxidative deamination of a variety of amine substrates. Observed rate constants are second order with respect to substrate and inhibitor (phenylhydrazine) concentration. Kinetic studies with para-substituted benzylamines and their dideuterated counterparts reveal KIEs (>6) larger than those observed with native AADH (KIEs similar to unity). This is attributed to formation of the benzylamine-derived iminoquinone requiring structural rearrangement of the benzyl side chain in the active site of the native enzyme. This structural reorganization requires motions from the side chains of adjacent residues (which are absent in the isolated small subunit). The position of Phe alpha 97 in particular is responsible for the conformational gating (and hence deflated KlEs) observed with Para-substituted benzylamines in the native enzyme. Hammett plots for the small subunit exhibit a strong correlation of structure-reactivity data with electronic substituent effects for para-substituted benzylamines and phenethylamines, unlike native AADH for which a poor correlation is observed. TTQ reduction in the isolated subunit is enhanced by electron withdrawing substituents, contrary to structure-reactivity studies reported for synthetic TTQ model compounds in which rate constants are enhanced by electron donating substituents. We infer that para-substituted benzylamines are good reactivity probes of TTQ mechanism with the isolated small subunit. This is attributed to the absence of structural rearrangement prior to H-transfer that limits the rate of TTQ reduction by para-substituted benzylamines in-native enzyme.
机译：对位取代的苄胺是与TTQ依赖的芳香胺脱氢酶（AADH）进行结构反应性研究的不良反应探针。在这项研究中，我们将动力学同位素效应（KIES）与结构反应性研究相结合，显示对位取代的苄胺是TTQ机制与AADH含TTQ的亚基分离的良好反应性探针。与具有催化活性的甲胺脱氢酶（MADH）含TTQ的亚基相反，AADH的小亚基可催化多种胺底物的氧化脱氨作用。相对于底物和抑制剂（苯肼）的浓度，观察到的速率常数是二阶的。用对位取代的苄胺及其双氘代对应物进行的动力学研究表明，KIEs（> 6）大于天然AADH（与统一性相似的KIEs）。这归因于形成苄胺衍生的亚氨基醌，其需要在天然酶的活性位点中苄基侧链的结构重排。这种结构重组需要相邻残基（在分离的小亚基中不存在）的侧链运动。 Phe alpha 97的位置尤其负责在天然酶中用对位取代的苄胺观察到的构象门控（因此是放气的Kle）。小亚基的哈米特图显示了结构反应性数据与对位取代的苄胺和苯乙胺的电子取代基效应有很强的相关性，与天然AADH的相关性很差。吸电子取代基增强了分离的亚基的TTQ还原，这与合成TTQ模型化合物报道的结构反应性研究相反，在合成TTQ模型化合物中，给电子取代基提高了速率常数。我们推断对位取代的苄胺是与分离的小亚基的TTQ机制的良好反应性探针。这归因于在H转移之前不存在结构重排，这限制了对位取代的苄胺天然酶对TTQ的还原速率。

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