A gene on chromosome 4q13.1 that encodes a sulfotransferase which may control oestrogen receptor levels by sulfating free oestradiol. It also sulfates dehydroepiandrosterone, pregnenolone, ethinylestradiol and various drugs.
Given the structural differences between 17(3-estradiol and the flame retardants, Pedersen says he was surprised the exogenous molecules were able to bind SULT1E1. Craig Butt, a postdoctoral environmental chemist at Duke University's Nicholas School of the Environment, observes, "It shows that there is a little bit of flexibility in terms of what molecules can fit into the enzyme, which explains why these foreign chemicals can inhibit the action of the enzyme."
Caption: TBBPA (pink) binds to same active site of the estrogen-metabolizing enzyme SULT1E1 (blue) as the body's major natural estrogen (transparent grey).
In the present study, we obtained crystal structures of SULT1E1 with the product cofactor adenosine-3-5-diphosphate (PAP) in complexes with the ubiquitous flame retardant TBBPA and a BFR metabolite, 3-OH-BDE-47.
In these experiments, we used the SULT1E1 mutant V269E [expressed and purified as described previously (Pedersen et al.
The structures were solved using the structure of SULT1E1 [Protein Data Bank (PDB; http://www.rcsb.org/pdb/home/home.
Although the OH-PCBs have low affinities for both [alpha] and [beta] estrogen receptors, some OH-PCBs are strikingly potent inhibitors of human estrogen sulfotransferase (SULT1E1), with subnanomolar concentrations that produced 50% inhibition (IC50) (Kester et al.
SULT1A1, SULT1B1, and SULT1E1 are the major phenol sulfotransferases expressed in human liver, with SULT1A1 (also known as ST1A3) found at the highest concentration (Honma et al.
The expression of human SULT1A1*1, SULT1A3, SULT1B1, and SULT1E1 in Escherichia coli has been described previously (Dajani et al.