caa a22 4500 605512671 CHVBK 20210128100656.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00894-015-2625-1 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2625-1 The effect of ligands on the thermal stability of sulfotransferases: a molecular dynamics simulation study [Elektronische Daten] [Pu-pu Zhang, Li Zhao, Shi-yang Long, Pu Tian] Human cytosolic sulfotransferases (hSULTs) are important phase II metabolic enzymes. They catalyze transfer of the sulfuryl-group (-SO3) from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to the hydroxyl or primary amine moieties of a large number of endogenous and xenobiotic substrates. Broad selectivity and specificity of binding and activity within the sulfortransferases family could be detected by thermal denaturation assays, which have been made more and more suitable for high throughput screening based on recent technical advances. Here molecular dynamics simulations were used to explore the effect of the cofactor (PAPS) and substrate (LCA) on the thermal stability of the enzyme. It was found that the apo-enzyme unfolded fastest upon heating. The holo-enzyme with bound substrate LCA unfolded slowest. This thermo-denaturation order is consistent with that observed in experiments. Further it was found that the cofactor and substrate will pronouncedly increase the thermal stability of the active pocket regions that interact directly with the ligands. In addition, cofactor and substrate show noticeable synergy effect on the thermal stability of the enzyme. Graphical Abstract Human cytosolic sulfotransferase 2A1 Springer-Verlag Berlin Heidelberg, 2015 Human cytosolic sulfotransferase 2A1 nationallicence Molecular dynamic simulations nationallicence Thermal stability nationallicence Zhang Pu-pu School of Life Sciences, Jilin University, Changchun, China aut Zhao Li School of Life Sciences, Jilin University, Changchun, China aut Long Shi-yang School of Life Sciences, Jilin University, Changchun, China aut Tian Pu School of Life Sciences, Jilin University, Changchun, China aut Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-7 1610-2940 21:4<1 2015 21 894 https://doi.org/10.1007/s00894-015-2625-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00894-015-2625-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Pu-pu School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Zhao Li School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Long Shi-yang School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Tian Pu School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 773 0- Journal of Molecular Modeling Springer Berlin Heidelberg 21/4(2015-04-01), 1-7 1610-2940 21:4<1 2015 21 894