Molecular probes for human cytochrome P450 enzymes: Recent progress and future perspectives

Molecular probes for human cytochrome P450 enzymes: Recent progress and future perspectives
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人细胞色素 P450 酶的分子探针:最新进展和未来展望

DOI:
10.1016/j.ccr.2020.213600
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发表时间:
2021-01
影响因子:
20.6
通讯作者:
Guangbo Ge
Guangbo Ge
中科院分区:
化学1区
文献类型:
--
作者:
Jingjing Wu;Xiaoqing Guan;Ziru Dai;Rongjing He;Xinxin Ding;Ling Yang;Guangbo Ge

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细胞色素P450酶(P450或CYPs)是一类含血红素的单加氧酶,负责多种内源性物质和外源化学物质的氧化代谢。破译CYPs的生理功能及其与人类疾病的相关性需要可靠的工具来感知复杂生物系统中的靶酶。在过去的几十年里,人们为开发人类CYP的异构体特异性探针底物做出了巨大的努力,并将其用于基础研究和转化应用。不断增长的人类CYP配体和3d结构数据库有力地促进了设计和开发具有更高特异性的CYP探针底物。本文就近年来人类CYPs分子探针的研究进展及应用作一综述。综述了人类CYP的结构和催化特性,以及开发CYP探针底物的设计原则和策略。本文介绍了两种用于各种人类CYP酶的分子探针,包括非光学探针和光学探针底物,以及它们的结构信息和动力学参数。最后,提出并强调了该领域当前面临的挑战和未来的展望。本文提供的信息和知识为传感复杂生物系统中的CYP活性、探索CYP与人类疾病的相关性以及筛选和表征CYP调节剂提供了实用工具。
The cytochrome P450 enzymes (P450s or CYPs) are a class of heme-containing monooxygenases responsible for the oxidative metabolism of a wide range of endogenous substances and foreign chemicals. Deciphering the physiological functions of CYPs and their relevance to human diseases requires reliable tools for sensing target enzyme in complex biological systems. Over the past few decades, great efforts have been made to develop isoform-specific probe substrates for human CYP(s) and use them in both basic researches and translational applications. The growing database of the ligands and 3D-structures of human CYPs strongly facilitates the design and development of CYP probe substrates with improved specificity. Herein, we summarize the recent progress in the development and applications of molecular probes for human CYPs. The structural and catalytic features of human CYPs, as well as the design principles and strategies used in the development of CYP probe substrates, have been well summarized. Two comprehensive lists of molecular probes for various human CYP enzymes, including non-optical and optical probe substrates, along with their structural information and kinetic parameters, are presented. Finally, the current challenges and future perspectives in this field are proposed and highlighted. The information and knowledge presented here provides practical tools for sensing CYP activities in complex biological systems, exploring the relevance of CYPs to human diseases, as well as screening and characterizing of CYP modulators.
结合蛋白质组学和化学探针检测对人肝微粒体中细胞色素 P450 亚型进行定量分析
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