Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate

Tomoki Ota, Akinobu Senoo, Masumi Shirakawa, Hiroshi Nonaka, Yutaro Saito, Sho Ito, Go Ueno, Satoru Nagatoishi, Kouhei Tsumoto, Shinsuke Sando

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number102036
JournaliScience
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 19 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate'. Together they form a unique fingerprint.

Cite this