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

Détails

ID Serval
serval:BIB_AA02AD236F60
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lack of Enantioselectivity in the SULT1A3-catalyzed Sulfoconjugation of Normetanephrine Enantiomers: An In Vitro and Computational Study.
Périodique
Chirality
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
2013
Peer-reviewed
Oui
Volume
25
Pages
28-34
Langue
anglais
Notes
Publication types: JOURNAL ARTICLE
Résumé
(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
Création de la notice
18/12/2012 19:27
Dernière modification de la notice
12/06/2021 6:33
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