Structure and inhibition mechanism of the human citrate transporter NaCT.

ABSTRACT: Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis^1-3. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate^4,5. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor-which binds

SUBMITTER: Sauer DB 

PROVIDER: S-EPMC7933130 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature