ß-Glucuronidases of opportunistic bacteria are the major contributors to xenobiotic-induced toxicity in the gut.
Sci Rep
; 8(1): 16372, 2018 11 06.
Article
em En
| MEDLINE
| ID: mdl-30401818
ABSTRACT
Gut bacterial ß-D-glucuronidases (GUSs) catalyze the removal of glucuronic acid from liver-produced ß-D-glucuronides. These reactions can have deleterious consequences when they reverse xenobiotic metabolism. The human gut contains hundreds of GUSs of variable sequences and structures. To understand how any particular bacterial GUS(s) contributes to global GUS activity and affects human health, the individual substrate preference(s) must be known. Herein, we report that representative GUSs vary in their ability to produce various xenobiotics from their respective glucuronides. To attempt to explain the distinct substrate preference, we solved the structure of a bacterial GUS complexed with coumarin-3-ß-D-glucuronide. Comparisons of this structure with other GUS structures identified differences in loop 3 (or the α2-helix loop) and loop 5 at the aglycone-binding site, where differences in their conformations, hydrophobicities and flexibilities appear to underlie the distinct substrate preference(s) of the GUSs. Additional sequence, structural and functional analysis indicated that several groups of functionally related gut bacterial GUSs exist. Our results pinpoint opportunistic gut bacterial GUSs as those that cause xenobiotic-induced toxicity. We propose a structure-activity relationship that should allow both the prediction of the functional roles of GUSs and the design of selective inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bactérias
/
Xenobióticos
/
Glucuronidase
/
Intestinos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Taiwan