Structure of arylamine N-acetyltransferase reveals a catalytic triad
Structure of arylamine N-acetyltransferase reveals a catalytic triad
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DOI：
10.1038/76783
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发表时间：
2000-07
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影响因子：
--
通讯作者：
J. Sinclair;J. Sandy;R. Delgoda;E. Sim;M. Noble
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文献类型：
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作者：
J. Sinclair;J. Sandy;R. Delgoda;E. Sim;M. Noble
芳胺N-乙酰转移酶（NAT）家族的酶在从大肠杆菌到人类的物种中发现。在人类中，已知它们负责许多芳胺和肼药物的乙酰化，并且它们与某些外来物质的致癌增强密切相关。在原核生物中，它们的底物特异性可能不同，该基因家族的成员与利福霉素生产过程中的酰胺合成途径有关。在这里，我们报告的晶体结构在2.8 μ m分辨率的一个代表性的成员，这个家庭从鼠伤寒沙门氏菌在存在和不存在的共价结合的产品类似物。该结构揭示了令人惊讶的机制信息，包括Cys-His-Asp催化三联体的存在。折叠可以用大致相等长度的三个结构域来描述，其中第二和第三结构域通过结构域间螺旋连接。前两个结构域，螺旋束和β-桶，使用与半胱氨酸蛋白酶超家族相同的结构基序组成催化三联体。
Enzymes of the arylamine N-acetyltransferase (NAT) family are found in species ranging from Escherichia coli to humans. In humans they are known to be responsible for the acetylation of a number of arylamine and hydrazine drugs, and they are strongly linked to the carcinogenic potentiation of certain foreign substances. In prokaryotes their substrate specificities may vary and members of the gene family have been linked to pathways including amide synthesis during rifamycin production. Here we report the crystal structure at 2.8 Å resolution of a representative member of this family from Salmonella typhimurium in the presence and absence of a covalently bound product analog. The structure reveals surprising mechanistic information including the presence of a Cys-His-Asp catalytic triad. The fold can be described in terms of three domains of roughly equal length with the second and third domains linked by an interdomain helix. The first two domains, a helical bundle and a β-barrel, make up the catalytic triad using a structural motif identical to that of the cysteine protease superfamily.