Lack of Enantioselectivity in the SULT1A3-catalyzed Sulfoconjugation of Normetanephrine Enantiomers: An In Vitro and Computational Study.

Details

Serval ID
serval:BIB_AA02AD236F60
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lack of Enantioselectivity in the SULT1A3-catalyzed Sulfoconjugation of Normetanephrine Enantiomers: An In Vitro and Computational Study.
Journal
Chirality
Author(s)
Grouzmann E., Gualtierotti J.B., Gerber-Lemaire S., Abid K., Brakch N., Pedretti A., Testa B., Vistoli G.
ISSN
1520-636X (Electronic)
ISSN-L
0899-0042
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
25
Pages
28-34
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
(1R)-Normetanephrine is the natural stereoisomeric substrate for sulfotransferase 1A3 (SULT1A3)-catalyzed sulfonation. Nothing appears known on the enantioselectivity of the reaction despite its potential significance in the metabolism of adrenergic amines and in clinical biochemistry. We confronted the kinetic parameters of the sulfoconjugation of synthetic (1R)-normetanephrine and (1S)-normetanephrine by recombinant human SULT1A3 to a docking model of each normetanephrine enantiomer with SULT1A3 and the 3'-phosphoadenosine-5'-phosphosulfate cofactor on the basis of molecular modeling and molecular dynamics simulations of the stability of the complexes. The K(M) , V(max) , and k(cat) values for the sulfonation of (1R)-normetanephrine, (1S)-normetanephrine, and racemic normetanephrine were similar. In silico models were consistent with these findings as they showed that the binding modes of the two enantiomers were almost identical. In conclusion, SULT1A3 is not substrate-enantioselective toward normetanephrine, an unexpected finding explainable by a mutual adaptability between the ligands and SULT1A3 through an "induced-fit model" in the catalytic pocket. Chirality, 00:000-000, 2012.© 2012 Wiley Periodicals, Inc.
Pubmed
Web of science
Create date
18/12/2012 19:27
Last modification date
20/08/2019 16:14
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