|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 274, Issue 53, 37862-37868, December 31, 1999
From the Department of Molecular and Cellular Pathology, University
of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY,
United Kingdom, the § Protein Science Unit, Glaxo Wellcome
Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY,
United Kingdom, ¶ Research Biomet, Glaxo Wellcome Research and
Development, Park Road, Ware SG12 0DP, United Kingdom, and the
Humans are one of the few species that produce
large amounts of catecholamine sulfates, and they have evolved a
specific sulfotransferase, SULT1A3 (M-PST), to catalyze the formation
of these conjugates. An orthologous protein has yet to be found in
other species. To further our understanding of the molecular basis for
the unique substrate selectivity of this enzyme, we have solved the
crystal structure of human SULT1A3, complexed with 3'-phosphoadenosine 5'-phosphate (PAP), at 2.5 Å resolution and carried out quantitative structure-activity relationship (QSAR) analysis with a series of
phenols and catechols. SULT1A3 adopts a similar fold to mouse estrogen
sulfotransferase, with a central five-stranded
X-ray Crystal Structure of Human Dopamine Sulfotransferase,
SULT1A3
MOLECULAR MODELING AND QUANTITATIVE STRUCTURE-ACTIVITY
RELATIONSHIP ANALYSIS DEMONSTRATE A MOLECULAR BASIS FOR
SULFOTRANSFERASE SUBSTRATE SPECIFICITY*
,
, Department of Pharmacy, Viikki Biocenter, University of
Helsinki, Helsinki 00014, Finland
-sheet surrounded by
-helices. SULT1A3 is a dimer in solution but crystallized with a
monomer in the asymmetric unit of the cell, although dimer interfaces
were formed by interaction across crystallographic 2-fold axes. QSAR
analysis revealed that the enzyme is highly selective for catechols,
and catecholamines in particular, and that hydrogen bonding groups and
lipophilicity (cLogD) strongly influenced Km. We
also investigated further the role of Glu146 in SULT1A3
using site-directed mutagenesis and showed that it plays a key role not
only in defining selectivity for dopamine but also in preventing many
phenolic xenobiotics from binding to the enzyme.
*
This work was supported by the Biotechnology and Biological
Sciences Research Council (to M. W. H. C.) and in part by Commission of the European Communities Grant BMH4-CT97-2621 (to M. W. H. C. and
J. T.) and by an equipment grant from the Wellcome Trust (to
M. W. H. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Present address: Structural Biology Division, Institute of Cancer
Research, Fulham Rd., Chelsea, London SW7 3RP, United Kingdom.
**
To whom correspondence should be addressed.: Dept. of Molecular and
Cellular Pathology, University of Dundee, Ninewells Hospital and
Medical School, Dundee DD1 9SY, United Kingdom. Tel.: 44-1382-632510; Fax: 44-1382-640320; E-mail: m.w.h.coughtrie@dundee.ac.uk.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Shi, S. S. Lamb, S. Bhat, T. Sulea, G. D. Wright, A. Matte, and M. Cygler Crystal Structure of StaL, a Glycopeptide Antibiotic Sulfotransferase from Streptomyces toyocaensis J. Biol. Chem., April 27, 2007; 282(17): 13073 - 13086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Hoff, P. G. Czyryca, M. Sun, T. S. Leyh, and A. C. Hengge Transition State of the Sulfuryl Transfer Reaction of Estrogen Sulfotransferase J. Biol. Chem., October 13, 2006; 281(41): 30645 - 30649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Gamage, A. Barnett, N. Hempel, R. G. Duggleby, K. F. Windmill, J. L. Martin, and M. E. McManus Human Sulfotransferases and Their Role in Chemical Metabolism Toxicol. Sci., March 1, 2006; 90(1): 5 - 22. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Eisenhofer, I. J. Kopin, and D. S. Goldstein Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine Pharmacol. Rev., September 1, 2004; 56(3): 331 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Sheng, A. Saxena, and M. W. Duffel INFLUENCE OF PHENYLALANINES 77 AND 138 ON THE STEREOSPECIFICITY OF ARYL SULFOTRANSFERASE IV Drug Metab. Dispos., May 1, 2004; 32(5): 559 - 565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Glatt, U. Pabel, W. Meinl, H. Frederiksen, H. Frandsen, and E. Muckel Bioactivation of the heterocyclic aromatic amine 2-amino-3-methyl-9H-pyrido [2,3-b]indole (MeA{alpha}C) in recombinant test systems expressing human xenobiotic-metabolizing enzymes Carcinogenesis, May 1, 2004; 25(5): 801 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Barnett, S. Tsvetanov, N. Gamage, J. L. Martin, R. G. Duggleby, and M. E. McManus Active Site Mutations and Substrate Inhibition in Human Sulfotransferase 1A1 and 1A3 J. Biol. Chem., April 30, 2004; 279(18): 18799 - 18805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen and X. Chen Arginine Residues in the Active Site of Human Phenol Sulfotransferase (SULT1A1) J. Biol. Chem., September 19, 2003; 278(38): 36358 - 36364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Taskinen, B. T. Ethell, P. Pihlavisto, A. M. Hood, B. Burchell, and M. W. H. Coughtrie CONJUGATION OF CATECHOLS BY RECOMBINANT HUMAN SULFOTRANSFERASES, UDP-GLUCURONOSYLTRANSFERASES, AND SOLUBLE CATECHOL O-METHYLTRANSFERASE: STRUCTURE-CONJUGATION RELATIONSHIPS AND PREDICTIVE MODELS Drug Metab. Dispos., September 1, 2003; 31(9): 1187 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. U. Gamage, R. G. Duggleby, A. C. Barnett, M. Tresillian, C. F. Latham, N. E. Liyou, M. E. McManus, and J. L. Martin Structure of a Human Carcinogen-converting Enzyme, SULT1A1. STRUCTURAL AND KINETIC IMPLICATIONS OF SUBSTRATE INHIBITION J. Biol. Chem., February 21, 2003; 278(9): 7655 - 7662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Chapman, M. C. Bryan, and C.-H. Wong Mechanistic studies of beta -arylsulfotransferase IV PNAS, February 4, 2003; 100(3): 910 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Pai, I. Oxendine, T. Sugahara, M. Suiko, Y. Sakakibara, and M.-C. Liu Structure-Function Relationships in the Stereospecific and Manganese-dependent 3,4-Dihydroxyphenylalanine/ Tyrosine-sulfating Activity of Human Monoamine-form Phenol Sulfotransferase, SULT1A3 J. Biol. Chem., January 10, 2003; 278(3): 1525 - 1532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Pai, K. Ohkimoto, Y. Sakakibara, M. Suiko, T. Sugahara, and M.-C. Liu Manganese Stimulation and Stereospecificity of the Dopa (3,4-Dihydroxyphenylalanine)/Tyrosine-sulfating Activity of Human Monoamine-form Phenol Sulfotransferase. KINETIC STUDIES OF THE MECHANISM USING WILD-TYPE AND MUTANT ENZYMES J. Biol. Chem., November 8, 2002; 277(46): 43813 - 43820. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Tulik, S. Chodavarapu, R. Edgar, L. Giannunzio, A. Langland, B. Schultz, and J. D. Beckmann Inhibition of Bovine Phenol Sulfotransferase (bSULT1A1) by CoA Thioesters. EVIDENCE FOR POSITIVE COOPERATIVITY AND INHIBITION BY INTERACTION WITH BOTH THE NUCLEOTIDE AND PHENOL BINDING SITES J. Biol. Chem., October 11, 2002; 277(42): 39296 - 39303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Strott Sulfonation and Molecular Action Endocr. Rev., October 1, 2002; 23(5): 703 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Genst, D. Areskoug, K. Decanniere, S. Muyldermans, and K. Andersson Kinetic and Affinity Predictions of a Protein-Protein Interaction Using Multivariate Experimental Design J. Biol. Chem., August 9, 2002; 277(33): 29897 - 29907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Pedersen, E. Petrotchenko, S. Shevtsov, and M. Negishi Crystal Structure of the Human Estrogen Sulfotransferase-PAPS Complex. EVIDENCE FOR CATALYTIC ROLE OF Ser137 IN THE SULFURYL TRANSFER REACTION J. Biol. Chem., May 10, 2002; 277(20): 17928 - 17932. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Eisenhofer Free or Total Metanephrines for Diagnosis of Pheochromocytoma: What Is the Difference? Clin. Chem., June 1, 2001; 47(6): 988 - 989. [Full Text] [PDF]
|
|
|
|
|
|
M. W. H. Coughtrie and L. E. Johnston Interactions between Dietary Chemicals and Human Sulfotransferases{---}Molecular Mechanisms and Clinical Significance Drug Metab. Dispos., April 1, 2001; 29(4): 522 - 528. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |