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Publication Abstract from PubMed

Bile acids play essential roles in facilitating the intestinal absorption of lipophilic nutrients as well as regulation of glucose, lipid, and energy homeostasis via activation of some receptors. Bile acids are cytotoxic, and consequently their concentrations are tightly controlled. A critical pathway for bile acid elimination and detoxification is sulfation. The pattern of bile acid sulfation differs by species. Sulfation preferentially occurs at the 3alpha-OH of bile acids in humans, but at the 7alpha-OH in mice. A recent study identified mouse cytosolic sulfotransferase 2A8 (mSULT2A8) as the major hepatic 7alpha-hydroxyl bile acid-sulfating enzyme. To elucidate the 7alpha-OH specific sulfation mechanism of mSULT2A8, instead of 3alpha-OH specific sulfation in humans, we determined a crystal structure of mSULT2A8 in complex with cholic acid, a major bile acid, and 3'-phosphoadenosine-5'-phosphate, the sulfate donor product. Our study shows that bile acid-binding mode of mSULT2A8 and how the enzyme holds the 7alpha-OH group of bile acids at the catalytic center, revealing that the mechanism underlying 7alpha-OH specific sulfation. The structure shows the substrate binds to mSULT2A8 in an orientation perpendicular to that of human 3alpha-hydroxyl bile acid-sulfotransferase (hSULT2A1). The structure of the complex provides new insight into species different bile acid metabolism.

The crystal structure of mouse SULT2A8 reveals the mechanism of 7alpha-hydroxyl, bile acid sulfation.,Teramoto T, Nishio T, Kurogi K, Sakakibara Y, Kakuta Y Biochem Biophys Res Commun. 2021 May 21;562:15-20. doi:, 10.1016/j.bbrc.2021.04.113. PMID:34030040^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.