Mechanistic studies of β-arylsulfotransferase IV

Eli Chapman, Marian C. Bryan, Chi Huey Wong

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various molecules including small-molecule drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-molecule inhibitors. A linear free-energy analysis in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by β-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Broønsted coefficients (βnuc and βlg) are +0.33 and -0.45, giving Leffler α values of 0.19 and 0.61 for the forward and reverse reactions, respectively.

Original languageEnglish (US)
Pages (from-to)910-915
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number3
DOIs
StatePublished - Feb 4 2003
Externally publishedYes

Fingerprint

tyrosine-ester sulfotransferase
Hydroxyl Radical
Sulfotransferases
Amines
Steroids
Carbohydrates
Hormones
Enzymes
Pharmaceutical Preparations
Proteins

Keywords

  • Linear free energy
  • Mechanism
  • Sulfotransferase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Mechanistic studies of β-arylsulfotransferase IV. / Chapman, Eli; Bryan, Marian C.; Wong, Chi Huey.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 3, 04.02.2003, p. 910-915.

Research output: Contribution to journalArticle

@article{42d2da9d56f94e53a1d9b3adc5ea4c90,
title = "Mechanistic studies of β-arylsulfotransferase IV",
abstract = "Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various molecules including small-molecule drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-molecule inhibitors. A linear free-energy analysis in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by β-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Bro{\o}nsted coefficients (βnuc and βlg) are +0.33 and -0.45, giving Leffler α values of 0.19 and 0.61 for the forward and reverse reactions, respectively.",
keywords = "Linear free energy, Mechanism, Sulfotransferase",
author = "Eli Chapman and Bryan, {Marian C.} and Wong, {Chi Huey}",
year = "2003",
month = "2",
day = "4",
doi = "10.1073/pnas.0337638100",
language = "English (US)",
volume = "100",
pages = "910--915",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "3",

}

TY - JOUR

T1 - Mechanistic studies of β-arylsulfotransferase IV

AU - Chapman, Eli

AU - Bryan, Marian C.

AU - Wong, Chi Huey

PY - 2003/2/4

Y1 - 2003/2/4

N2 - Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various molecules including small-molecule drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-molecule inhibitors. A linear free-energy analysis in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by β-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Broønsted coefficients (βnuc and βlg) are +0.33 and -0.45, giving Leffler α values of 0.19 and 0.61 for the forward and reverse reactions, respectively.

AB - Sulfotransferases are an important class of enzymes that catalyze the transfer of a sulfuryl group to a hydroxyl or amine moiety on various molecules including small-molecule drugs, steroids, hormones, carbohydrates, and proteins. They have been implicated in a number of disease states but remain poorly understood, complicating the design of specific, small-molecule inhibitors. A linear free-energy analysis in both the forward and reverse directions indicates that the transfer of a sulfuryl group to an aryl hydroxyl group catalyzed by β-arylsulfotransferase IV likely proceeds by a dissociative (sulfotrioxide-like) mechanism. Values for the Broønsted coefficients (βnuc and βlg) are +0.33 and -0.45, giving Leffler α values of 0.19 and 0.61 for the forward and reverse reactions, respectively.

KW - Linear free energy

KW - Mechanism

KW - Sulfotransferase

UR - http://www.scopus.com/inward/record.url?scp=0037417971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037417971&partnerID=8YFLogxK

U2 - 10.1073/pnas.0337638100

DO - 10.1073/pnas.0337638100

M3 - Article

C2 - 12547913

AN - SCOPUS:0037417971

VL - 100

SP - 910

EP - 915

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 3

ER -