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Reaction product affinity regulates activation of human sulfotransferase 1A1 PAP sulfation

Authors
  • Tyapochkin, Eduard
  • Kumar, Vidya Prasanna
  • Cook, Paul F.
  • Chen, Guangping
Type
Published Article
Journal
Archives of Biochemistry and Biophysics
Publisher
Elsevier BV
Publication Date
Jan 01, 2010
Volume
506
Issue
2
Pages
137–141
Identifiers
DOI: 10.1016/j.abb.2010.11.018
Source
Elsevier
Keywords
License
Unknown

Abstract

Cytosolic sulfotransferase (SULT)-catalyzed sulfation regulates the activity of bio-signaling molecules and aids in metabolizing hydroxyl-containing xenobiotics. The sulfuryl donor for the SULT reaction is adenosine 3′-phosphate 5′-phosphosulfate (PAPS), while products are adenosine 3′,5′-diphosphate (PAP) and a sulfated alcohol. Human phenol sulfotransferase (SULT1A1) is one of the major detoxifying enzymes for phenolic xenobiotics. The mechanism of SULT1A1-catalyzed sulfation of PAP by pNPS was investigated. PAP was sulfated by para-nitrophenyl sulfate (pNPS) in a concentration-dependent manner. 2-Naphthol inhibited sulfation of PAP, competing with pNPS, while phenol activated the sulfation reaction. At saturating PAP, a ping pong kinetic mechanism is observed with pNPS and phenol as substrates, consistent with phenol intercepting the E–PAPS complex prior to dissociation of PAPS. At high concentrations, phenol competes with pNPS, consistent with formation of the E–PAP–phenol dead-end complex. Data are consistent with the previously reported mechanism for sulfation of 2-naphthol by PAPS, and its activation by pNPS [14]. Overall, data are consistent with release of PAP from E–PAP and PAPS from E–PAPS contributing to rate-limitation in both reaction directions.

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