7SVF

Bile salt hydrolase A from Lactobacillus gasseri with taurine bound

7SVF の概要

• エントリーDOI: 10.2210/pdb7svf/pdb
• 分子名称: Choloylglycine hydrolase, 2-AMINOETHANESULFONIC ACID, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: bile salt hydrolase, hydrolase
• 由来する生物種: Lactobacillus gasseri
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 144019.83

構造登録者

Walker, M.E.,Redinbo, M.R. (登録日: 2021-11-19, 公開日: 2023-01-25, 最終更新日: 2023-10-25)

主引用文献

Foley, M.H.,Walker, M.E.,Stewart, A.K.,O'Flaherty, S.,Gentry, E.C.,Patel, S.,Beaty, V.V.,Allen, G.,Pan, M.,Simpson, J.B.,Perkins, C.,Vanhoy, M.E.,Dougherty, M.K.,McGill, S.K.,Gulati, A.S.,Dorrestein, P.C.,Baker, E.S.,Redinbo, M.R.,Barrangou, R.,Theriot, C.M.
Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut.
Nat Microbiol, 8:611-628, 2023

PubMed Abstract: Bile acids (BAs) mediate the crosstalk between human and microbial cells and influence diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate selectivity and impact on C. difficile remain elusive. Here we survey the diversity of BSHs in the gut commensals Lactobacillaceae, which are commonly used as probiotics, and other members of the human gut microbiome. We structurally pinpoint a loop that predicts BSH preferences for either glycine or taurine substrates. BSHs with varying specificities were shown to restrict C. difficile spore germination and growth in vitro and colonization in pre-clinical in vivo models of CDI. Furthermore, BSHs reshape the pool of microbial conjugated bile acids (MCBAs) in the murine gut, and these MCBAs can further restrict C. difficile virulence in vitro. The recognition of conjugated BAs by BSHs defines the resulting BA pool, including the expansive MCBAs. This work provides insights into the structural basis of BSH mechanisms that shape the BA landscape and promote colonization resistance against C. difficile.

PubMed: 36914755
DOI: 10.1038/s41564-023-01337-7

実験手法

X-RAY DIFFRACTION (2.05 Å)