6EC6

Ruminococcus gnavus Beta-glucuronidase

6EC6 の概要

• エントリーDOI: 10.2210/pdb6ec6/pdb
• 分子名称: Beta-glucuronidase, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: glycosyl hydrolase, 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: 145303.78

構造登録者

Biernat, K.A.,Redinbo, M.R. (登録日: 2018-08-07, 公開日: 2019-02-13, 最終更新日: 2023-10-11)

主引用文献

Biernat, K.A.,Pellock, S.J.,Bhatt, A.P.,Bivins, M.M.,Walton, W.G.,Tran, B.N.T.,Wei, L.,Snider, M.C.,Cesmat, A.P.,Tripathy, A.,Erie, D.A.,Redinbo, M.R.
Structure, function, and inhibition of drug reactivating human gut microbial beta-glucuronidases.
Sci Rep, 9:825-825, 2019

PubMed Abstract: Bacterial β-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-β-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous to that found in E. coli GUS, which processes drug substrates. We also resolve the structure of the No Loop GUS from Bacteroides dorei. We then compare the pNPG and diclofenac glucuronide processing abilities of a panel of twelve structurally diverse GUS proteins, and find that the new L1 GUS enzymes presented here process small glucuronide substrates inefficiently compared to previously characterized L1 GUS enzymes like E. coli GUS. We further demonstrate that our GUS inhibitors, which are effective against some L1 enzymes, are not potent towards all. Our findings pinpoint active site structural features necessary for the processing of drug-glucuronide substrates and the inhibition of such processing.

PubMed: 30696850
DOI: 10.1038/s41598-018-36069-w

実験手法

X-RAY DIFFRACTION (2.85 Å)