標題: Modeling the binding and inhibition mechanism of nucleotides and sulfotransferase using molecular docking
作者: Lin, ES
Yang, JM
Yang, YS
生物科技學系
生物資訊及系統生物研究所
Department of Biological Science and Technology
Institude of Bioinformatics and Systems Biology
關鍵字: phenol sulfotransferase;3 '-phosphoadenosine 5 '-phosphosulfate;adenosine 3 ',5 '-bisphosphate;nucleotide
公開日期: 1-Jun-2003
摘要: Phenol sulfotransferase (PST) catalyzes sulfuryl group transfer from adenosine 3'-phosphate 5'-phosphosulfate (PAPS) to a variety of nucleophilic acceptors in biological systems. Physiological sulfation by PAPS results in the production of adenosine 3',5'-diphosphate (PAP). PAP may become a strong inhibitor or cofactor for the physiological or the transfer reactions, respectively. Several nucleotides other than, PAP also serve as substrates, inhibitors or cofactors of PST catalyzed reactions. We are interested in the effects of these nucleotides on the PST catalyzed reactions and their possible physiological significance in biology. Several nucleotide inhibitors (such as adenosine 5'-diphosphate and adenosine 5'-triphosphate) of sulfotransferase in physiological reactions have been reported in the literature. However, our data suggests that they are not inhibitors for the transfer reaction or the reverse physiological reaction catalyzed by PST. The aim of this work is to show that the molecular docking analysis can be successfully used to underline the inhibition mechanism of these nucleotides. First, the selected compounds were subjected to a detailed docking analysis, by means of GEMDOCK, a program able to reveal the most likely binding mode for each ligand. By comparing these results with binding sites and binding compounds of the nucleotides with known X-ray structures, it is possible to highlight the site specificity and the inhibition mechanism of the select compounds. The results obtained by the above algorithm were further confirmed experimentally. In this paper, we show the effect of a variety of nucleotides on the activity of sulfotransferase in different docking conditions.
URI: http://hdl.handle.net/11536/27806
ISSN: 0009-4536
期刊: JOURNAL OF THE CHINESE CHEMICAL SOCIETY
Volume: 50
Issue: 3B
起始頁: 655
結束頁: 663
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