Boolean Logic Networks Mimicked with Chimeric Enzymes Activated/Inhibited by Several Input Signals.,ChemPhysChem

当前位置： X-MOL 学术 › ChemPhysChem › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Boolean Logic Networks Mimicked with Chimeric Enzymes Activated/Inhibited by Several Input Signals.
ChemPhysChem ( IF 2.3 ) Pub Date : 2019-12-12 , DOI: 10.1002/cphc.201901050
Paolo Bollella ₁ , Madhura Bellare ₁ , Vasantha Krishna Kadambar ₁ , Zhong Guo ₂ , Kirill Alexandrov ₂ , Artem Melman ₁ , Evgeny Katz ₁

Affiliation

Reactions catalyzed by artificial allosteric enzymes, chimeric proteins with fused biorecognition and catalytic units, were used to mimic multi‐input Boolean logic systems. The catalytic parts of the systems were represented by pyrroloquinoline quinone‐dependent glucose dehydrogenase (PQQ‐GDH). Two biorecognition units, calmodulin or artificial peptide‐clamp, were integrated into PQQ‐GDH and locked it in the OFF or ON state respectively. The ligand‐peptide binding cooperatively with Ca²⁺ cations to a calmodulin bioreceptor resulted in the enzyme activation, while another ligand‐peptide bound to a clamp‐receptor inhibited the enzyme. The enzyme activation and inhibition originated from peptide‐induced allosteric transitions in the receptor units that propagated to the catalytic domain. While most of enzymes used to mimic Boolean logic gates operate with two inputs (substrate and co‐substrate), the used chimeric enzymes were controlled by four inputs (glucose – substrate, dichlorophenolindophenol – electron acceptor/co‐substrate, Ca²⁺ cations and a peptide – activating/inhibiting signals). The biocatalytic reactions controlled by four input signals were considered as logic networks composed of several concatenated logic gates. The developed approach allows potentially programming complex logic networks operating with various biomolecular inputs representing potential utility for different biomedical applications.

中文翻译：

由几种输入信号激活/抑制的嵌合酶模仿的布尔逻辑网络。

人工变构酶，具有融合生物识别功能的嵌合蛋白和催化单元催化的反应被用来模拟多输入布尔逻辑系统。该系统的催化部分由吡咯并喹啉醌依赖性葡萄糖脱氢酶（PQQ‐GDH）代表。将钙调蛋白或人工肽夹两个生物识别单元整合到PQQ-GDH中，并将其分别锁定在OFF或ON状态。配体-肽与Ca ²⁺协同结合钙调蛋白生物受体的阳离子导致酶活化，而与钳位受体结合的另一种配体肽则抑制了该酶。酶的激活和抑制来自于肽诱导的受体单元的变构转变，该构象转变传播至催化结构域。虽然大多数用于模拟布尔逻辑门的酶都有两个输入（底物和共底物），但使用的嵌合酶却受四个输入控制（葡萄糖–底物，二氯酚吲哚酚–电子受体/共底物，Ca ²⁺阳离子和一种肽–激活/抑制信号）。由四个输入信号控制的生物催化反应被认为是由几个串联的逻辑门组成的逻辑网络。所开发的方法允许对使用各种生物分子输入进行操作的复杂逻辑网络进行潜在编程，这些逻辑网络表示针对不同生物医学应用的潜在效用。

更新日期：2019-12-12

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11