9BS5

Bacteroides ovatus GH97C Sus

Summary for 9BS5

• Entry DOI: 10.2210/pdb9bs5/pdb
• Descriptor: Alpha-glucosidase, 4,6-dideoxy-4-{[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)cyclohex-2-en-1-yl]amino}-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose, 1,2-ETHANEDIOL, ... (9 entities in total)
• Functional Keywords: glycoside hydrolase family 97, gh97, bacteroides ovatus, susb, hydrolase
• Biological source: Bacteroides ovatus ATCC 8483
• Total number of polymer chains: 2
• Total formula weight: 168038.20

Authors

Brown, H.A.,Koropatkin, N.M. (deposition date: 2024-05-13, release date: 2024-10-30, Last modification date: 2025-05-14)

Primary citation

Brown, H.A.,Morris, A.L.,Pudlo, N.A.,Hopkins, A.E.,Martens, E.C.,Golob, J.L.,Koropatkin, N.M.
Acarbose impairs gut Bacteroides growth by targeting intracellular glucosidases.
Mbio, 15:e0150624-e0150624, 2024

PubMed Abstract: Acarbose is a type 2 diabetes medicine that prevents dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading , (Bo), and (Bt). Bt growth on starch polysaccharides is severely impaired by acarbose, whereas Bo growth is much less affected by the drug. The use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the TonB-dependent SusC proteins and binds to the Sus transcriptional regulators. Furthermore, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in , including variation between related species. Furthermore, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes.

PubMed: 39565129
DOI: 10.1128/mbio.01506-24

Experimental method

X-RAY DIFFRACTION (1.46 Å)