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Rapid CommunicationAccelerated Communication

A Single Amino Acid, Glu146, Governs the Substrate Specificity of a Human Dopamine Sulfotransferase, SULT1A3

Rana Dajani, Alan M. Hood and Michael W. H. Coughtrie
Molecular Pharmacology December 1998, 54 (6) 942-948; DOI: https://doi.org/10.1124/mol.54.6.942
Rana Dajani
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
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Alan M. Hood
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
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Michael W. H. Coughtrie
Department of Molecular and Cellular Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, UK
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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.

Footnotes

    • Received August 17, 1998.
    • Accepted September 10, 1998.
  • Send reprint requests to: Dr. M. W. H. Coughtrie, Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, Scotland, UK. E-mail: m.w.h.coughtrie{at}dundee.ac.uk

  • This work was supported by the Biotechnology and Biological Sciences Research Council, the Commission of the European Communities (BMH4-CT97–2621) and by an equipment grant from the Wellcome Trust.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 54 (6)
Molecular Pharmacology
Vol. 54, Issue 6
1 Dec 1998
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Rapid CommunicationAccelerated Communication

A Single Amino Acid, Glu146, Governs the Substrate Specificity of a Human Dopamine Sulfotransferase, SULT1A3

Rana Dajani, Alan M. Hood and Michael W. H. Coughtrie
Molecular Pharmacology December 1, 1998, 54 (6) 942-948; DOI: https://doi.org/10.1124/mol.54.6.942

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Rapid CommunicationAccelerated Communication

A Single Amino Acid, Glu146, Governs the Substrate Specificity of a Human Dopamine Sulfotransferase, SULT1A3

Rana Dajani, Alan M. Hood and Michael W. H. Coughtrie
Molecular Pharmacology December 1, 1998, 54 (6) 942-948; DOI: https://doi.org/10.1124/mol.54.6.942
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