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PMID:9855620
| Citation |
Dajani, R, Hood, AM and Coughtrie, MW (1998) A single amino acid, glu146, governs the substrate specificity of a human dopamine sulfotransferase, SULT1A3. Mol. Pharmacol. 54:942-8 |
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| Abstract |
Sulfation, catalyzed by members of the sulfotransferase (SULT) superfamily, exerts considerable influence over the biological activity of numerous endogenous and xenobiotic chemicals. In humans, catecholamines such as dopamine are extensively sulfated, and a SULT isoform (SULT1A3 or the monoamine-sulfating form of phenolsulfotransferase) has evolved with considerable selectivity for dopamine and other biogenic amines. To investigate the molecular basis for this selectivity, we identified a region of SULT1A3, which, we hypothesized, contributes to its preference for biogenic amines, and mutated two amino acids within this domain to the corresponding residues in a closely related but functionally distinct phenol sulfotransferase, SULT1A1 (H143Y and E146A). The change of a single amino acid, E146A, was sufficient to transform the catalytic properties and substrate preference of SULT1A3, such that they closely resembled those of SULT1A1. These experiments confirm the functional role of Glu146 in the selectivity of SULT1A3 for biogenic amines and suggest that this region is a key determinant of sulfotransferase substrate specificity. |
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| Keywords |
Amino Acid Sequence; Arylsulfotransferase/chemistry; Arylsulfotransferase/genetics; Arylsulfotransferase/metabolism; Binding Sites; Cloning, Molecular; Glutamic Acid/chemistry; Glutamic Acid/metabolism; Histidine/chemistry; Humans; Isoenzymes/chemistry; Isoenzymes/genetics; Isoenzymes/metabolism; Kinetics; Molecular Sequence Data; Mutagenesis, Site-Directed; Substrate Specificity |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0004062: aryl sulfotransferase activity |
ECO:0000315: |
F |
Figure 3 compares the dopamine sulfotransferase activity for SULT1A3 wild type and mutants. |
complete | ||||
|
enables |
GO:0004062: aryl sulfotransferase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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