Three structurally and functionally distinct β-glucuronidases from the human gut microbe Bacteroides uniformis

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Human gut microbiome glycoside hydrolases process diverse glycoconjugates.
• Beta-glucuronidases (GUS) are key enzymes in this process.
• Understanding microbial enzyme diversity is crucial for drug metabolism and glycan processing.

Purpose of the Study:

• To characterize three distinct beta-glucuronidase (GUS) enzymes from Bacteroides uniformis.
• To elucidate the structural basis for functional differences in these GUS enzymes.
• To investigate their roles in processing polysaccharides and SN-38-glucuronide.

Main Methods:

• X-ray crystallography (nine structures)
• Biochemical assays
• Biophysical analyses

Main Results:

• Identified three structurally and functionally unique GUS active sites from B. uniformis.
• Demonstrated differential processing of glucuronic acid-containing polysaccharides and SN-38-glucuronide.
• Showcased the impact of quaternary structure on active site distinctiveness.

Conclusions:

• Highlights significant structural and functional diversity of GUS enzymes within a single gut commensal.
• Advances understanding of how microbial enzyme structure dictates substrate specificity (glycans, drug metabolites).
• Provides insights into potential modulation of drug efficacy (e.g., irinotecan) by gut microbes.