Crystal structure of human sulfotransferase SULT1A3 in complex with dopamine and 3'-phosphoadenosine 5'-phosphate.
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.
Lu
Jing-Hua
JH
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Bejing 100101, PR China.
Li
Hai-Tao
HT
Liu
Ming-Cheh
MC
Zhang
Ji-Ping
JP
Li
Mei
M
An
Xiao-Min
XM
Chang
Wen-Rui
WR
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*
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