Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3′-phosphoadenosine 5′-phosphate
Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3′-phosphoadenosine 5′-phosphate
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DOI：
10.1016/j.bbrc.2005.07.091
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发表时间：
2005-09-23
影响因子：
3.1
通讯作者：
Chang, WR
中科院分区：
文献类型：
--
作者：
Lu, JH;Li, HT;Chang, WR
人磺基转移酶SULT 1A 3特异性催化单胺如多巴胺、肾上腺素和去甲肾上腺素的磺化。SULT 1A 3还具有独特的3，4-二羟基苯丙氨酸（多巴）/酪氨酸硫酸化活性，其优先朝向其D-型对映异构体，并且可以被Mn 2+显著刺激。为了进一步了解这种酶独特底物特异性的分子基础，我们以2.6埃分辨率解析了与多巴胺和3 '-磷酸腺苷5'-磷酸复合的人SULT 1A 3的晶体结构，并用（D）-多巴进行了自动对接分析。SULT 1A 3酶-配体复合物的结构清楚地表明残基Glu 146可以与多巴胺形成静电相互作用，并且可能在立体选择性和硫酸化活性中起关键作用。另一方面，残基Asp 86似乎是至关重要的Mn 2+刺激的多巴/酪氨酸硫酸化活性的SULT 1A 3，除了在立体选择性和硫酸化活性的支持作用。(c)2005年爱思唯尔公司All rights reserved.
The human sulfotransferase, SULT1A3, catalyzes specifically the sulfonation of monoamines such as dopamine, epinephrine, and norepinephrine. SULT1A3 also has a unique 3,4-di hydroxyphenylalanine (Dopa)/tyrosine-sulfating activity that is preferentially toward their D-form enantiomers and can be stimulated dramatically by Mn2+. To further our understanding of the molecular basis for the unique substrate specificity of this enzyme, we solved the crystal structure of human SULT1A3, complexed with dopamine and 3'-phosphoadenosine 5'-phosphate, at 2.6 angstrom resolution and carried out autodocking analysis with (D)-Dopa. The structure of SULT1A3 enzyme-ligand complex clearly showed that residue Glu146 can form electrostatic interaction with dopamine and may play a pivotal role in the stereoselectivity and sulfating activity. On the other hand, residue Asp86 appeared to be critical to the Mn2+-stimulation of the Dopa/tyrosine-sulfating activity of SULT1A3, in addition to a supporting role in the stereo selectivity and sulfating activity. (c) 2005 Elsevier Inc. All rights reserved.