Δ4-3-ketosteroids as a new class of substrates for the cytosolic sulfotransferases

Takuyu Hashiguchi, Katsuhisa Kurogi, Takehiko Shimohira, Takamasa Teramoto, Ming Cheh Liu, Masahito Suiko, Yoichi Sakakibara

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)2883-2890
Number of pages8
JournalBiochimica et Biophysica Acta - General Subjects
Volume1861
Issue number11
DOIs
Publication statusPublished - Nov 2017

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

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