Identifying androsterone (ADT) as a cognate substrate for human dehydroepiandrosterone sulfotransferase (DHEA-ST) important for steroid homeostasis
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In steroid biosynthesis, human dehydroepiandrosterone sulfotransferase (DHEA-ST) in the adrenals has been reported to catalyze the transfer of the sulfonate group from 3′-phosphoadenosine-5′-phosphosulfate to dehydroepiandrosterone (DHEA). DHEA and its sulfate play roles as steroid precursors; however, the role of the enzyme in the catabolism of androgens is poorly understood. Androsterone sulfate is clinically recognized as one of the major androgen metabolites found in urine. Here it is demonstrated that this enzyme recognizes androsterone (ADT) as a cognate substrate with similar kinetics but a 2-fold specificity and stronger substrate inhibition than DHEA. The structure of human DHEA-ST in complex with ADT has been solved at 2.7 Å resolution, confirming ADT recognition. Structural analysis has revealed the binding mode of ADT differs from that of DHEA, despite the similarity of the overall structure between the ADT and the DHEA binary complexes. Our results identify that this human enzyme is an ADT sulfotransferase as well as a DHEA sulfotransferase, implying an important role in steroid homeostasis for the adrenals and liver.
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SULT2A2 can target 3α- and 17β-hydroxyl groups and has been shown to sulfate An, testosterone and DHT.
“SULT2A2 can target 3α- and 17β-hydroxyl groups and has been shown to sulfate An, testosterone and DHT [294,295].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [295]
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References 31 · Cited by 1
Research works printed but not linked: 2
- Milgrom, E. (1990) in Steroid Hormones (Baulieu, E-E., and Kelly, P. A., eds) pp. 398 -402, Chapman and Hall, New York and London
- Cornish-Bowden, A. (1995) Analysis of Enzyme Kinetic Data, pp. 118 -122, Oxford University Press, Oxford
- Authors
- Chang, H.-J., Shi, R., Rehse, P., & Lin, S.-X.
- Affiliations
- Centre hospitalier de l'Université Laval (CA)
- Corresponding author
- Lin, Sheng-Xiang
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 279
- Issue
- 4
- Pages
- 2689-2696
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1513210259
- Cited by
- 1
- References
- 31
- FWCI
- 0.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
- Science
- Funders
- Canadian Space Agency
- Canadian Institutes of Health Research
- Brookhaven National Laboratory
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- androsterone, dehydroepiandrosterone sulfotransferase, substrate specificity, substrate inhibition, enzyme kinetics, enzyme-substrate complex structure, androgen metabolism, adrenal cortex, liver, sulfotransferase
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