期刊
ISCIENCE
卷 24, 期 2, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102036
关键词
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资金
- CREST [JPMJCR13L4]
- Japan Science and Technology Agency
- JSPS KAKENHI [19H00919]
- JSPS [JP18H02082, JM16H02420, JP19H05766]
- Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED [JP19am0101001, JP19am0101094]
Bile acids play a crucial role in lipid digestion and absorption in the small bowel, as well as regulating their own metabolism and impacting other biological systems. The study suggests that secondary bile acid conjugates may act as modulators of serine hydroxymethyltransferase activity.
Bile acids are metabolites of cholesterol that facilitate lipid digestion and absorption in the small bowel. Bile acids work as agonists of receptors to regulate their own metabolism. Bile acids also regulate other biological systems such as sugar metabolism, intestinal multidrug resistance, and adaptive immunity. However, numerous physiological roles of bile acids remain undetermined. In this study, we solved the crystal structure of human serine hydroxymethyltransferase (hSHMT) in complex with an endogenous secondary bile acid glycine conjugate. The specific interaction between hSHMT and the ligand was demonstrated using mutational analyses, biophysical measurements, and structure-activity relationship studies, suggesting that secondary bile acid conjugates may act as modulators of SHMT activity.
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