6JZ4

b-glucuronidase from Ruminococcus gnavus in complex with D-glucaro-d-lactam

6JZ4 の概要

• エントリーDOI: 10.2210/pdb6jz4/pdb
• 分子名称: Beta-glucuronidase, (2S,3R,4S,5R)-3,4,5-trihydroxy-6-oxopiperidine-2-carboxylic acid, (4R)-2-METHYLPENTANE-2,4-DIOL, ... (4 entities in total)
• 機能のキーワード: b-glucuronidase, hydrolase
• 由来する生物種: Ruminococcus gnavus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 146038.06

構造登録者

Dashnyam, P.,Lin, H.Y. (登録日: 2019-04-30, 公開日: 2020-06-03, 最終更新日: 2024-03-27)

主引用文献

Dashnyam, P.,Lin, H.Y.,Chen, C.Y.,Gao, S.,Yeh, L.F.,Hsieh, W.C.,Tu, Z.,Lin, C.H.
Substituent Position of Iminocyclitols Determines the Potency and Selectivity for Gut Microbial Xenobiotic-Reactivating Enzymes.
J.Med.Chem., 63:4617-4627, 2020

PubMed Abstract: Selective inhibitors of gut bacterial β-glucuronidases (GUSs) are of particular interest in the prevention of xenobiotic-induced toxicities. This study reports the first structure-activity relationships on potency and selectivity of several iminocyclitols (-) for the GUSs. Complex structures of GUS with - explained how charge, conformation, and substituent of iminocyclitols affect their potency and selectivity. N1 of uronic isofagomine () made strong electrostatic interactions with two catalytic glutamates of GUSs, resulting in the most potent inhibition ( ≥ 11 nM). C6-propyl analogue of () displayed 700-fold selectivity for opportunistic bacterial GUSs ( = 74 nM for GUS and 51.8 μM for GUS). In comparison with , there was 200-fold enhancement in the selectivity, which was attributed to differential interactions between the propyl group and loop 5 residues of the GUSs. The results provide useful insights to develop potent and selective inhibitors for undesired GUSs.

PubMed: 32105467
DOI: 10.1021/acs.jmedchem.9b01918

実験手法

X-RAY DIFFRACTION (1.712 Å)