6D41

Bacteriodes uniformis beta-glucuronidase 1 bound to D-glucaro-1,5-lactone

6D41 の概要

• エントリーDOI: 10.2210/pdb6d41/pdb
• 分子名称: Beta-galactosidase/beta-glucuronidase, GLYCEROL, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Bacteroides uniformis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 141388.91

構造登録者

Walton, W.G.,Pellock, S.J.,Redinbo, M.R. (登録日: 2018-04-17, 公開日: 2018-10-17, 最終更新日: 2023-10-04)

主引用文献

Pellock, S.J.,Walton, W.G.,Biernat, K.A.,Torres-Rivera, D.,Creekmore, B.C.,Xu, Y.,Liu, J.,Tripathy, A.,Stewart, L.J.,Redinbo, M.R.
Three structurally and functionally distinct beta-glucuronidases from the human gut microbeBacteroides uniformis.
J. Biol. Chem., 293:18559-18573, 2018

PubMed Abstract: The glycoside hydrolases encoded by the human gut microbiome play an integral role in processing a variety of exogenous and endogenous glycoconjugates. Here we present three structurally and functionally distinct β-glucuronidase (GUS) glycoside hydrolases from a single human gut commensal microbe, We show using nine crystal structures, biochemical, and biophysical data that whereas these three proteins share similar overall folds, they exhibit different structural features that create three structurally and functionally unique enzyme active sites. Notably, quaternary structure plays an important role in creating distinct active site features that are hard to predict via structural modeling methods. The enzymes display differential processing capabilities toward glucuronic acid-containing polysaccharides and SN-38-glucuronide, a metabolite of the cancer drug irinotecan. We also demonstrate that GUS-specific and nonselective inhibitors exhibit varying potencies toward each enzyme. Together, these data highlight the diversity of GUS enzymes within a single gut commensal and advance our understanding of how structural details impact the specific roles microbial enzymes play in processing drug-glucuronide and glycan substrates.

PubMed: 30301767
DOI: 10.1074/jbc.RA118.005414

実験手法

X-RAY DIFFRACTION (1.9 Å)