Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening.
Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening.
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通过同源性建模和虚拟筛选引导的二肽分配酶酶促功能的发现。
DOI：
10.1016/j.str.2008.08.015
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发表时间：
2008-11-12
期刊：
影响因子：
--
通讯作者：
Jacobson MP
中科院分区：
文献类型：
--
作者：
Kalyanaraman C;Imker HJ;Fedorov AA;Fedorov EV;Glasner ME;Babbitt PC;Almo SC;Gerlt JA;Jacobson MP
我们已经开发了一种计算方法来帮助指定未表征的蛋白质的酶功能，该方法使用同源建模来预测结合位点的结构，并在电子对接中识别潜在的底物。我们将这种方法应用于功能多样化的烯醇化酶超家族中与枯草芽孢杆菌L-丙氨酸-D/L-葡萄糖异构体酶同源的蛋白质。特别是，来自Thermotoga martima的一种蛋白质被预测具有不同的底物专一性，这表明它具有不同的生物学功能，但尚不清楚。这一预测得到了实验的证实，从而指定了L-丙氨酸-D/L-Phe、L-丙氨酸-D/L-Tyr和L-丙氨酸-D/L-His的异构酶活性，但在GenBank中该酶被错误地注释为变锥酸环异构酶。随后，确定了该酶与三种底物的络合物的晶体结构，与计算模型吻合较好，揭示了观察到的底物选择性的结构基础。
We have developed a computational approach to aid the assignment of enzymatic function for uncharacterized proteins that uses homology modeling to predict the structure of the binding site and in silico docking to identify potential substrates. We apply this method to proteins in the functionally diverse enolase superfamily that are homologous to the characterized L-Ala-D/L-Glu epimerase from Bacillus subtilis. In particular, a protein from Thermotoga martima was predicted to have different substrate specificity, which suggests that it has a different, but as yet unknown, biological function. This prediction was experimentally confirmed, resulting in the assignment of epimerase activity for L-Ala-D/L-Phe, L-Ala-D/L-Tyr, and L-Ala-D/L-His, whereas the enzyme is annotated incorrectly in GenBank as muconate cycloisomerase. Subsequently, crystal structures of the enzyme were determined in complex with three substrates, showing close agreement with the computational models and revealing the structural basis for the observed substrate selectivity.
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影响因子：
2.9
作者：
Pegg, SCH;Brown, SD;Babbitt, PC
通讯作者：
Babbitt, PC
影响因子：
46.9
作者：
Macchiarulo, A;Nobeli, I;Thornton, JM
通讯作者：
Thornton, JM
影响因子：
5.6
作者：
Favia, Angelo D.;Nobeli, Irene;Thornton, Janet M.
通讯作者：
Thornton, Janet M.
影响因子：
5.8
作者：
Polacco, BJ;Babbitt, PC
通讯作者：
Babbitt, PC
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL