6M5O

Co-crystal structure of human serine hydroxymethyltransferase 2 in complex with Pyridoxal 5'-phosphate (PLP) and glycodeoxycholic acid

Summary for 6M5O

• Entry DOI: 10.2210/pdb6m5o/pdb
• Descriptor: Serine hydroxymethyltransferase, mitochondrial, (3ALPHA,5BETA,12ALPHA)-3,12-DIHYDROXYCHOLAN-24-OIC ACID, GLYCINE, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 113620.89

Authors

Ota, T.,Senoo, A.,Ito, S.,Ueno, G.,Nagatoishi, S.,Tsumoto, K.,Sando, S. (deposition date: 2020-03-11, release date: 2021-01-20, Last modification date: 2023-11-29)

Primary citation

Ota, T.,Senoo, A.,Shirakawa, M.,Nonaka, H.,Saito, Y.,Ito, S.,Ueno, G.,Nagatoishi, S.,Tsumoto, K.,Sando, S.
Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate.
Iscience, 24:102036-102036, 2021

PubMed 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.

PubMed: 33521601
DOI: 10.1016/j.isci.2021.102036

Experimental method

X-RAY DIFFRACTION (2.30000663987 Å)