title: Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate.
abstract: The human sulfotransferase, SULT1A3, catalyzes specifically the sulfonation of monoamines such as dopamine, epinephrine, and norepinephrine. SULT1A3 also has a unique 3,4-dihydroxyphenylalanine (Dopa)/tyrosine-sulfating activity that is preferentially toward their D-form enantiomers and can be stimulated dramatically by Mn2+. To further our understanding of the molecular basis for the unique substrate specificity of this enzyme, we solved the crystal structure of human SULT1A3, complexed with dopamine and 3'-phosphoadenosine 5'-phosphate, at 2.6 A resolution and carried out autodocking analysis with D-Dopa. The structure of SULT1A3 enzyme-ligand complex clearly showed that residue Glu146 can form electrostatic interaction with dopamine and may play a pivotal role in the stereoselectivity and sulfating activity. On the other hand, residue Asp86 appeared to be critical to the Mn2+-stimulation of the Dopa/tyrosine-sulfating activity of SULT1A3, in addition to a supporting role in the stereoselectivity and sulfating activity.
authors.affiliation: National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Bejing 100101, PR China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Lu
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Li
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
authors.forename: Ji-Ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: An
authors.forename: Wen-Rui
authors.initials: WR
authors.lastname: Chang
mesh_terms: D000244:Adenosine Diphosphate / Q000737:chemistry*; D020816:Amino Acid Motifs; D015239:Arylsulfotransferase; D001224:Aspartic Acid / Q000737:chemistry; D018360:Crystallography, X-Ray; D004298:Dopamine / Q000737:chemistry*; D005973:Glutamine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008345:Manganese / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity; D013237:Stereoisomerism; D015238:Sulfotransferases / Q000737:chemistry*
chemical_list: D008024:Ligands; D005973:Glutamine; D001224:Aspartic Acid; D008345:Manganese; D000244:Adenosine Diphosphate; C010840:adenosine 3'-phosphate-5'-phosphate; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C403170:monoamine-sulfating phenol sulfotransferase; D004298:Dopamine