Human cytosolic sulfotransferase SULT1A1
Human cytosolic sulfotransferase SULT1A1
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DOI：
10.1016/j.biocel.2006.10.002
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
McManus, Michael E.
中科院分区：
文献类型：
--
作者：
Hempel, Nadine;Gamage, Niranjali;McManus, Michael E.
磺化是一系列生物过程（包括II期代谢）所需的重要缀合反应，其中磺基缀合使化合物更具亲水性以帮助其排泄。负责异生物质磺化的主要酶是广泛表达的胞质磺基转移酶SULT 1A 1。SULT 1A 1晶体结构提供了对这种酶的底物特异性和催化功能的见解，包括其在内源性底物（如雌激素）磺化中的作用。与其代谢作用相反，SULT 1A 1也可以生物活化化合物;已知它可以磺化致癌物，如羟甲基多环芳烃，导致能够形成DNA加合物的高活性中间体，可能导致诱变。鉴于SULT 1A 1在这些不同功能中的作用以及具有不同催化活性的等位基因变体的发现，这种酶一直是众多多态性研究的焦点，这些研究调查了个体间SULT 1A 1变异与各种癌症病因之间的联系。(c)2006爱思唯尔有限公司版权所有。
Sulfonation is an important conjugation reaction required for a range of biological processes including phase II metabolism, whereby sulfo-conjugation renders a compound more hydrophilic to aid its excretion. The major enzyme responsible for xenobiotic sulfonation is the widely expressed cytosolic sulfotransferase SULT1A1. The SULT1A1 crystal structure has provided insights into this enzyme's substrate specificity and catalytic function, including its role in the sulfonation of endogenous substrates such as oestrogens. Contrary to its metabolic role, SULT1A1 can also bioactivate compounds; it is known to sulfonate pro-carcinogens such as hydroxymethyl polycyclic aromatic hydrocarbons leading to highly reactive intermediates capable of forming DNA adducts, potentially resulting in mutagenesis. Given the role of SULT1A1 in these diverse functions and the discovery of allefic variants with differing catalytic activities, this enzyme has been the focus of numerous polymorphic studies investigating the link between inter-individual SULT1A1 variance and the etiology of a variety of cancers. (c) 2006 Elsevier Ltd. All rights reserved.