caa a22 4500 605513066 CHVBK 20210128100658.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s00894-015-2739-5 doi (NATIONALLICENCE)springer-10.1007/s00894-015-2739-5 The impact of ligands on the structure and flexibility of sulfotransferases: a molecular dynamics simulation study [Elektronische Daten] [Li Zhao, Pupu Zhang, Shiyang Long, Linlin Wang, Pu Tian] Sulfotransferases catalyze transfer of the sulfuryl-group (-SO3) from 3′-phosphoadenosine 5′-phosphosulfate (PAPS) to a large number of substrates. They play an important role in phase II metabolic process. The impact of the cofactor (PAPS) on the structure and flexibility of the enzyme has been studied extensively, and the response of the active-cap region to cofactor binding was proposed as the molecular basis for substrate selectivity. In this study, individual and cooperative effects of the cofactor and substrate on the structure and flexibility of the enzyme were investigated. Molecular dynamics simulations were performed for four systems, including free enzyme, binary complexes (cofactor or substrate bound enzyme) and ternary complex (both cofactor and substrate bound enzyme). The influence of ligands (the cofactor and the substrate) on the structure and flexibility of the enzyme, especially that of the active-site cap region, was analyzed. Moreover, mutual structural impact of the ligands was examined as well. The results show that the impact of both the cofactor and the substrate was significant. Our study indicated that the substrate, such as lithocholic acid (LCA), participated in regulating the structure and flexibility of the enzyme actively rather than merely being selected passively. Additionally, the observed synergistic effects of the cofactor and the substrate demonstrated the importance of examining both ligands in understanding enzymes. Springer-Verlag Berlin Heidelberg, 2015 Cofactor and substrate nationallicence Human cytosolic sulfotransferase 2A1 nationallicence Molecular dynamics simulation nationallicence Structure and flexibility nationallicence Zhao Li School of Life Sciences, Jilin University, Changchun, China aut Zhang Pupu School of Life Sciences, Jilin University, Changchun, China aut Long Shiyang School of Life Sciences, Jilin University, Changchun, China aut Wang Linlin 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 21/8(2015-08-01), 1-9 1610-2940 21:8<1 2015 21 894 https://doi.org/10.1007/s00894-015-2739-5 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/s00894-015-2739-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhao Li School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Zhang Pupu School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Long Shiyang School of Life Sciences, Jilin University, Changchun, China aut NATIONALLICENCE 700 1- Wang Linlin 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 21/8(2015-08-01), 1-9 1610-2940 21:8<1 2015 21 894