Hanzlik Robert P, Fang Jianwen, Koen Yakov M
Department of Medicinal Chemistry and Bioinformatics Core Facility, University of Kansas, Lawrence, 66045-7582, USA.
Chem Biol Interact. 2009 Apr 15;179(1):38-44. doi: 10.1016/j.cbi.2008.08.016. Epub 2008 Sep 6.
The post-translational modification of proteins is a well-known endogenous mechanism for regulating protein function and activity. Cellular proteins are also susceptible to post-translational modification by xenobiotic agents that possess, or whose metabolites possess, significant electrophilic character. Such non-physiological modifications to endogenous proteins are sometimes benign, but in other cases they are strongly associated with, and are presumed to cause, lethal cytotoxic consequences via necrosis and/or apoptosis. The Reactive Metabolite Target Protein Database (TPDB) is a searchable, freely web-accessible (http://tpdb.medchem.ku.edu:8080/protein_database/) resource that attempts to provide a comprehensive, up-to-date listing of known reactive metabolite target proteins. In this report we characterize the TPDB by reviewing briefly how the information it contains came to be known. We also compare its information to that provided by other types of "-omics" studies relevant to toxicology, and we illustrate how bioinformatic analysis of target proteins may help to elucidate mechanisms of cytotoxic responses to reactive metabolites.
蛋白质的翻译后修饰是一种众所周知的调节蛋白质功能和活性的内源性机制。细胞蛋白质也容易受到具有显著亲电特性的外源性物质或其代谢产物的翻译后修饰。这种对内源性蛋白质的非生理性修饰有时是良性的，但在其他情况下，它们与坏死和/或凋亡导致的致命细胞毒性后果密切相关，并被认为会引发这些后果。反应性代谢物靶蛋白数据库（TPDB）是一个可搜索的、可通过网络免费访问的资源（http://tpdb.medchem.ku.edu:8080/protein_database/），它试图提供一份全面、最新的已知反应性代谢物靶蛋白列表。在本报告中，我们通过简要回顾其所含信息是如何被知晓的来对TPDB进行特征描述。我们还将其信息与毒理学相关的其他类型“组学”研究提供的信息进行比较，并举例说明对靶蛋白的生物信息学分析如何有助于阐明对反应性代谢物的细胞毒性反应机制。
