8BLT

Structure of Lactobacillus salivarius (Ls) bile salt hydrolase(BSH) in complex with taurocholate (TCA)

8BLT の概要

• エントリーDOI: 10.2210/pdb8blt/pdb
• 分子名称: Bile salt hydrolase, TAUROCHOLIC ACID (3 entities in total)
• 機能のキーワード: bile salt hydrolase, taurocholate, tca, hydrolase
• 由来する生物種: Ligilactobacillus salivarius
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 298605.81

構造登録者

Karlov, D.S.,Long, S.L.,Zeng, X.,Xu, F.,Lal, K.,Cao, L.,Hayoun, K.,Lin, J.,Joyce, S.A.,Tikhonova, I.G. (登録日: 2022-11-10, 公開日: 2023-03-08, 最終更新日: 2024-02-07)

主引用文献

Karlov, D.S.,Long, S.L.,Zeng, X.,Xu, F.,Lal, K.,Cao, L.,Hayoun, K.,Lin, J.,Joyce, S.A.,Tikhonova, I.G.
Characterization of the mechanism of bile salt hydrolase substrate specificity by experimental and computational analyses.
Structure, 31:629-, 2023

PubMed Abstract: Bile salt hydrolases (BSHs) are currently being investigated as target enzymes for metabolic regulators in humans and as growth promoters in farm animals. Understanding structural features underlying substrate specificity is necessary for inhibitor design. Here, we used a multidisciplinary workflow including mass spectrometry, mutagenesis, molecular dynamic simulations, machine learning, and crystallography to demonstrate substrate specificity in Lactobacillus salivarius BSH, the most abundant enzyme in human and farm animal intestines. We show the preference of substrates with a taurine head and a dehydroxylated sterol ring for hydrolysis. A regression model that correlates the relative rates of hydrolysis of various substrates in various enzyme mutants with the residue-substrate interaction energies guided the identification of structural determinants of substrate binding and specificity. In addition, we found T208 from another BSH protomer regulating the hydrolysis. The designed workflow can be used for fast and comprehensive characterization of enzymes with a broad range of substrates.

PubMed: 36963397
DOI: 10.1016/j.str.2023.02.014

実験手法

X-RAY DIFFRACTION (2.1 Å)