title: Investigating the substrate binding mechanism of sulfotransferase 2A1 based on substrate tunnel analysis: a molecular dynamics simulation study.
abstract: Cytosolic sulfotransferases (SULTs) catalyze the transfer of a sulfonate group from the unique cofactor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a large number of diverse substrates. In this work, tunnels that facilitate the transport of substrates in the enzyme were studied, with and without bound cofactor, using extensive molecular dynamics simulations. Residues making up tunnels, as well as residues forming bottlenecks to the tunnels, were identified. Conformation analysis of the active-site cap was also performed. We found that binding of cofactor could significantly narrow the tunnel based on the closing of the active-site cap to the enzyme. The roles of the key residues identified in this work deserve further exploration experimentally.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Jilin University, Changchun, China.|Zhongshan Ophthalmic Center, Sun Yat-Sen University, Zhongshan, China.
authors.forename: Pupu
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Long
authors.affiliation: School of Life Sciences, Jilin University, Changchun, China.|Ultrasound Department, China-Japan Union Hospital of Jilin University, Changchun, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun, China.
authors.forename: Hanyong
authors.initials: H
authors.lastname: Jin
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Han
authors.affiliation: School of Life Sciences, Jilin University, Changchun, China. tianpu@jlu.edu.cn.|Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun, China. tianpu@jlu.edu.cn.
authors.forename: Pu
authors.initials: P
authors.lastname: Tian
keywords: Molecular dynamics simulation; SULT2A1; Substrate binding mechanism; Tunnel analysis