Journal:Acta Cryst D:S2059798320015004

The substrate binding in the bile acid transporter ASBT_Yf of Yersinia frederiksenii

Xiaodong Wang, Ying Lyu, Yujia Ji, Ziyi Sun and Xiaoming Zhou ^[1]

Molecular Tour
Apical sodium-dependent bile acid transporter (ASBT) recycles bile acids from small intestine into enterocytes, and is a potential drug target for treating several metabolic diseases including type 2 diabetes. However, where and how bile acids bind in ASBT is unknown, which hampers our understanding toward its working mechanism.

In this study, four structures of an ASBT protein, called ASBT_Yf, are determined. In these structures, several ligand-like acid molecules, including a citrate, a glycine and a sulfate, bind in a putative substrate-binding pocket of the protein. The structural data are consistent with a computational model the defines the substrate-binding site, and support the binding pattern of bile acids. Functional analysis further validates the computational bile acid binding model, which provides structural insights toward its transport mechanism.

References

1. ↑ Wang X, Lyu Y, Ji Y, Sun Z, Zhou X. Substrate binding in the bile acid transporter ASBTYf from Yersinia frederiksenii. Acta Crystallogr D Struct Biol. 2021 Jan 1;77(Pt 1):117-125. doi:, 10.1107/S2059798320015004. Epub 2021 Jan 1. PMID:33404531 doi:http://dx.doi.org/10.1107/S2059798320015004