Journal article
Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: Studies on the formation of catalytically non-productive enzyme complexes
Archives of biochemistry and biophysics, Vol.507(2), pp.232-240
03/15/2011
DOI: 10.1016/j.abb.2010.12.027
PMCID: PMC3058861
PMID: 21187059
Abstract
The cytosolic sulfotransferase hSULT2A1 is the major hydroxysteroid (alcohol) sulfotransferase in human liver, and it catalyzes the 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfation of various endogenous hydroxysteroids as well as many xenobiotics that contain alcohol and phenol functional groups. The hSULT2A1 often displays substrate inhibition, and we have hypothesized that a key element in this response to increasing substrate concentration is the formation of non-productive ternary dead-end enzyme complexes involving the nucleotide product, adenosine 3',5'-diphosphate (PAP). One of these substrates for hSULT2A1 is dehydroepiandrosterone (DHEA), a major circulating steroid hormone in humans that serves as precursor to both androgens and estrogens. We have utilized DHEA in both initial velocity studies and equilibrium binding experiments in order to evaluate the potential role of ternary complexes in substrate inhibition of the enzyme. Our results indicate that hSULT2A1 forms non-productive ternary complexes that involve either DHEA or dehydroepiandrosterone sulfate, and the formation of these ternary complexes displays negative cooperativity in the binding of DHEA. (C) 2010 Elsevier Inc. All rights reserved.
Details
- Title: Subtitle
- Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: Studies on the formation of catalytically non-productive enzyme complexes
- Creators
- Hayrettin Ozan Gulcan - University of IowaMichael W. Duffel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Archives of biochemistry and biophysics, Vol.507(2), pp.232-240
- DOI
- 10.1016/j.abb.2010.12.027
- PMID
- 21187059
- PMCID
- PMC3058861
- NLM abbreviation
- Arch Biochem Biophys
- ISSN
- 0003-9861
- eISSN
- 1096-0384
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- R01CA038683 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 CA038683 / National Institutes of Health, National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P42 ES013661; P30 ES05605 / National Institute of Environmental Health Sciences, NIEHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) P30ES005605 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Language
- English
- Date published
- 03/15/2011
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984285537902771
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