Insight into glucocorticoids glucosylation by glucosyltransferase: A combined experimental and in-silico approach.

Cortisone Glucocorticoids Glucose Glucosides Glucosyltransferases / chemistry Prednisone
Cortisone Enzymatic glucosylation Glucocorticoids Molecular dynamics simulation Prednisone

Journal

Biophysical chemistry
ISSN: 1873-4200
Titre abrégé: Biophys Chem
Pays: Netherlands
ID NLM: 0403171

Informations de publication

Date de publication:
10 2022
Historique:
received: 05 06 2022
revised: 06 08 2022
accepted: 06 08 2022
pubmed: 21 8 2022
medline: 9 9 2022
entrez: 20 8 2022
Statut: ppublish

Résumé

Glucosyltransferases catalyze the glucosidic bond formation by transferring a glucose molecule from an activated sugar donor to an acceptor substrate. Glucocorticoids (GCs) are adrenal-derived steroid hormones most widely used for anti-inflammatory treatments. In this study, we biotransformed two selected GCs, cortisone and prednisone, into their O-glucoside derivatives using a versatile UDP-glycosyltransferase UGT-1. Complete structural assignment of glucosylated products revealed that the bioconversion by regio-selective glucosylation of cortisone and prednisone produced cortisone 21-glucoside and prednisone 21-glucoside, respectively. We also combined molecular dynamics (MD) simulation to study the binding feature and mechanism of glucosylation. MD simulation studies showed the formation of a stable complex between protein, glucose donor, and substrate, stabilized by hydrogen bonds. Overall, we were able to provide explanations for the experimentally observed selectivity for glucosylation by integrating experimental and computational techniques.

Identifiants

DOI: 10.1016/j.bpc.2022.106875 PMID: 35987098
pubmed: 35987098
pii: S0301-4622(22)00117-X
doi: 10.1016/j.bpc.2022.106875
pii:
doi:

Substances chimiques

Glucocorticoids 0
Glucosides 0
Glucosyltransferases EC 2.4.1.-
Glucose IY9XDZ35W2
Cortisone V27W9254FZ
Prednisone VB0R961HZT

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106875

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that there are no conflicts of interest.

Auteurs

Pradeep Subedi (P)

Department of Life Science and Biochemical Engineering, Sunmoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea.

Min-Su Kim (MS)

Department of Life Science and Biochemical Engineering, Sunmoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea.

Joo-Ho Lee (JH)

Genome-based BioIT Convergence Institute, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea; Department of BT-Convergent Pharmaceutical Engineering, Sunmoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea.

Jong Kook Park (JK)

Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, 1 Hallymdaehak-gil, Chuncheon, Gangwon-do 24252, Republic of Korea.

Tae-Jin Oh (TJ)

Department of Life Science and Biochemical Engineering, Sunmoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea; Genome-based BioIT Convergence Institute, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea; Department of BT-Convergent Pharmaceutical Engineering, Sunmoon University, 70 Sunmoon-ro 221, Tangjeong-myeon, Asan-si, Chungnam 31460, Republic of Korea. Electronic address: tjoh3782@sunmoon.ac.kr.

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Classifications MeSH

questionsmedicales.fr › Hormones corticosurrénaliennes › Hydroxycorticostéroïdes › 17-Hydroxycorticostéroïdes › Cortisone › Insight into glucocorticoids glucosylation by...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hormones, substituts d'hormones et antagonistes d'hormones › Hormones › Glucocorticoïdes › Insight into glucocorticoids glucosylation by...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Glucose › Insight into glucocorticoids glucosylation by...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides › Insight into glucocorticoids glucosylation by...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Hexosyltransferases › Glucosyltransferases › Insight into glucocorticoids glucosylation by...
questionsmedicales.fr › Composés polycycliques › Composés à cycles fusionnés › Stéroïdes › Prégnanes › Prégnadiènes › Prégnadiènediols › Prednisone › Insight into glucocorticoids glucosylation by...