Biochemistry Seminar: Da-Neng Wang, "Structure and inhibition mechanism of the human liver citrate transporter NaCT"
| When |
Apr 14, 2021
from 12:00 PM to 01:00 PM |
|---|---|
| Where | Via Zoom |
| Contact Name | Lauren Gohara |
| Contact Phone | 212-650-8803 |
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ZOOM LINK:
https://gc-cuny-edu.zoom.us/j/88065912335
Meeting ID: 880 6591 2335
ABSTRACT
Citrate is most well-known as an intermediate in the TCA 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. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic citrate concentration. Liver cells import citrate via the sodium-dependent citrate transporter NaCT (SLC13A5), and as a consequence this protein is a potential target for anti-obesity drugs. To understand the structural basis of its inhibition mechanism, we have determined cryo-electron microscopy structures of human NaCT in complex with citrate and with a small molecule inhibitor. These structures reveal how the inhibitor, bound at the same site as citrate, arrests the protein’s transport cycle. The NaCT-inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity.
