The protein arginine deiminases: Structure, function, inhibition, and disease.
The protein arginine deiminases: Structure, function, inhibition, and disease.
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DOI：
10.1002/bip.22127
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发表时间：
2013-02
期刊：
影响因子：
2.9
通讯作者：
Thompson, Paul R.
中科院分区：
文献类型：
--
作者：
Bicker, Kevin L.;Thompson, Paul R.
组蛋白的翻译后修饰对染色质的整体功能有重要影响。一种这样的修饰是瓜氨酸，其由蛋白质精氨酸脱亚胺酶（PAD）催化，所述蛋白质精氨酸脱亚胺酶是催化肽基精氨酸水解以在组蛋白、纤维蛋白原和其他生物相关蛋白质上形成肽基瓜氨酸的独特酶家族。在几种疾病中观察到过表达和/或增加的PAD活性，包括类风湿性关节炎、阿尔茨海默病、多发性硬化、狼疮、帕金森病和癌症。本文综述了PAD的重要结构和机制特征，以及最近的研究PAD在RA和结肠炎中增加疾病严重程度的作用，以及PAD活性在介导中性粒细胞胞外陷阱（NET）形成通过染色质去凝聚的重要性。最后，讨论了开发具有优异效价、选择性和体内功效的PAD抑制剂的努力，重点介绍了最有前途的抑制剂。
The post translational modification of histones has significant effects on overall chromatin function. One such modification is citrullination, which is catalyzed by the protein arginine deiminases (PADs), a unique family of enzymes that catalyzes the hydrolysis of peptidyl-arginine to form peptidyl-citrulline on histones, fibrinogen, and other biologically relevant proteins. Overexpression and/or increased PAD activity is observed in several diseases, including rheumatoid arthritis, Alzheimer’s disease, multiple sclerosis, lupus, Parkinson’s disease, and cancer. This review discusses the important structural and mechanistic characteristics of the PADs, as well as recent investigations into the role of the PADs in increasing disease severity in RA and colitis and the importance of PAD activity in mediating neutrophil extracellular trap (NET) formation through chromatin decondensation. Lastly, efforts to develop PAD inhibitors with excellent potency, selectivity and in vivo efficacy are discussed, highlighting the most promising inhibitors.
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影响因子：
3.7
作者：
Hemmers S;Teijaro JR;Arandjelovic S;Mowen KA
通讯作者：
Mowen KA
DOI：
10.1038/nrrheum.2011.132
发表时间：
2011-09-27
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.3
作者：
Causey, Corey P.;Jones, Justin E.;Slack, Jessica L.;Kamei, Daisuke;Jones, Larry E., Jr.;Subramanian, Venkataraman;Knuckley, Bryan;Ebrahimi, Pedram;Chumanevich, Alexander A.;Luo, Yuan;Hashimoto, Hiroshi;Sato, Mamoru;Hofseth, Lorne J.;Thompson, Paul R.
通讯作者：
Thompson, Paul R.
影响因子：
3.8
作者：
Chang X;Han J;Pang L;Zhao Y;Yang Y;Shen Z
通讯作者：
Shen Z
DOI：
10.1006/bbrc.2001.6303
发表时间：
2002-01-25
影响因子：
3.1
作者：
Hagiwara, T;Nakashima, K;Yamada, M
通讯作者：
Yamada, M