TY - JOUR
T1 - Δ4-3-ketosteroids as a new class of substrates for the cytosolic sulfotransferases
AU - Hashiguchi, Takuyu
AU - Kurogi, Katsuhisa
AU - Shimohira, Takehiko
AU - Teramoto, Takamasa
AU - Liu, Ming Cheh
AU - Suiko, Masahito
AU - Sakakibara, Yoichi
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Numbers 23580138 (M.S.), 21580114 (Y.S.), 15H04502 (Y.S.), 17H05028 (K.K.) and for JSPS Research Fellows Grant Number 24･1404 (T.H.) and National Institutes of Health grant R03HD071146 (M.C.L.).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/11
Y1 - 2017/11
N2 - Cytosolic sulfotransferase (SULT)-mediated sulfation is generally known to involve the transfer of a sulfonate group from the active sulfate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to a hydroxyl group or an amino group of a substrate compound. We report here that human SULT2A1, in addition to being able to sulfate dehydroepiandrosterone (DHEA) and other hydroxysteroids, could also catalyze the sulfation of Δ4-3-ketosteroids, which carry no hydroxyl groups in their chemical structure. Among a panel of Δ4-3-ketosteroids tested as substrates, 4-androstene-3,17-dione and progesterone were found to be sulfated by SULT2A1. Mass spectrometry analysis and structural modeling supported a reaction mechanism which involves the isomerization of Δ4-3-ketosteroids from the keto form to an enol form, prior to being subjected to sulfation. Results derived from this study suggested a potential role of SULT2A1 as a Δ4-3-ketosteroid sulfotransferase in steroid metabolism.
AB - Cytosolic sulfotransferase (SULT)-mediated sulfation is generally known to involve the transfer of a sulfonate group from the active sulfate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to a hydroxyl group or an amino group of a substrate compound. We report here that human SULT2A1, in addition to being able to sulfate dehydroepiandrosterone (DHEA) and other hydroxysteroids, could also catalyze the sulfation of Δ4-3-ketosteroids, which carry no hydroxyl groups in their chemical structure. Among a panel of Δ4-3-ketosteroids tested as substrates, 4-androstene-3,17-dione and progesterone were found to be sulfated by SULT2A1. Mass spectrometry analysis and structural modeling supported a reaction mechanism which involves the isomerization of Δ4-3-ketosteroids from the keto form to an enol form, prior to being subjected to sulfation. Results derived from this study suggested a potential role of SULT2A1 as a Δ4-3-ketosteroid sulfotransferase in steroid metabolism.
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U2 - 10.1016/j.bbagen.2017.08.005
DO - 10.1016/j.bbagen.2017.08.005
M3 - Article
C2 - 28782626
AN - SCOPUS:85027727007
SN - 0304-4165
VL - 1861
SP - 2883
EP - 2890
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 11
ER -