Mouse N-acetyltransferase type 2, the homologue of human N-acetyltransferase type 1.
Mouse N-acetyltransferase type 2, the homologue of human N-acetyltransferase type 1.
复制标题
小鼠N-乙酰转移酶2型，人类N-乙酰转移酶类型1的同源物。
DOI：
10.1016/j.bcp.2007.12.012
复制
发表时间：
2008-04-01
影响因子：
5.8
通讯作者：
Sim, Edith
中科院分区：
文献类型：
--
作者：
Kawamura, Akane;Westwood, Isaac;Wakefield, Larissa;Long, Hilary;Zhang, Naixia;Walters, Kylie;Redfield, Christina;Sim, Edith
关键词：
越来越多的证据表明，人芳胺N-乙酰转移酶1(NAT1，EC 2.3.1.5)虽然首次被鉴定为药物代谢酶的同源物，但似乎是人类雌激素受体阳性乳腺癌的标志。老鼠Nat2相当于人类的Nat1。乳腺癌小鼠模型的建立是非常重要的，探索小鼠Nat2的生物学作用也是非常必要的。因此，我们生产了小鼠Nat2作为重组蛋白，并研究了其底物特异谱，并与人Nat1进行了比较。此外，我们还测试了抑制剂对小鼠NAT2的影响，包括内源性和外源性类固醇化合物。我们发现他莫昔芬、染料木素和己烯雌酚对小鼠的Nat2有抑制作用。类固醇类似物双酚A也抑制小鼠Nat2酶的活性，核磁共振光谱显示，通过质子峰的移动，结合接近活性部位。最近公布了人类Nat1的三维结构，我们已经使用这种晶体结构生成了小鼠Nat2结构的模型。我们认为，为了使配体与蛋白质的活性部位结合，需要在结构上发生构象变化。
There is increasing evidence that human arylamine N-acetyltransferase type 1 (NAT1, EC 2.3.1.5), although first identified as a homologue of a drug-metabolising enzyme, appears to be a marker in human oestrogen receptor positive breast cancer. Mouse Nat2 is the mouse equivalent of human NAT1. The development of mouse models of breast cancer is important, and it is essential to explore the biological role of mouse Nat2. We have therefore produced mouse Nat2 as a recombinant protein and have investigated its substrate specificity profile in comparison with human NAT1. In addition, we have tested the effects of inhibitors on mouse Nat2, including compounds which are endogenous and exogenous steroids. We show that tamoxifen, genistein and diethylstilbestrol inhibit mouse Nat2. The steroid analogue, bisphenol A, also inhibits mouse Nat2 enzymic activity and is shown by NMR spectroscopy, through shifts in proton peaks, to bind close to the active site. A three-dimensional structure for human NAT1 has recently been released, and we have used this crystal structure to generate a model of the mouse Nat2 structure. We propose that a conformational change in the structure is required in order for ligands to bind to the active site of the protein.
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DOI：
10.1073/pnas.96.16.9212
发表时间：
1999-08-03
影响因子：
11.1
作者：
Perou, CM;Jeffrey, SS;Botstein, D
通讯作者：
Botstein, D
影响因子：
50.3
作者：
Richardson, AL;Wang, ZGC;Ganesan, S
通讯作者：
Ganesan, S
影响因子：
5.6
作者：
Fullam, Elizabeth;Westwood, Isaac M.;Noble, Martin E. M.
通讯作者：
Noble, Martin E. M.
影响因子：
4.8
作者：
Mushtaq, A;Payton, M;Sim, E
通讯作者：
Sim, E
影响因子：
2.8
作者：
Payton, M;Mushtaq, A;Sim, E
通讯作者：
Sim, E