Nature Chen Lei's group reported that the hypoglycemic drug Enpagliflozin inhibits human SGLT2-MAP...

Glucose is one of the most important energy sources for most living things on the earth

The main protein responsible for glucose reabsorption in the kidney is sodium-glucose cotransporter (SGLT), which is a member of the solute carrier transporter 5A (solute carrier transporter 5A), which is completely different from GLUT (SLC2A) ²

Based on the structure of the natural product phloridin, a variety of specific inhibitors of SGLT2 have been successfully developed and used clinically to treat type 2 diabetes, such as Empagliflozin and Canagliflozin (Canagliflozin), dapagliflozin (dapagliflozin,) and the like ⁸ , wherein englitazone net is selective for SGLT2 SGLT1 2500 times ⁹

On December 8,

The molecular weight of

Figure 1.

SGLT2 is a 14-pass transmembrane protein, of which TM1-10 is the core structure of transport, TM1-5 and TM6-10 are topologically inverted repeat structures, the core structure of transport and the prokaryotic leucine transporter (LeuT) Similar

Figure 2.

The inhibitor Enpagliflozin binds in the middle of the SGLT2 protein.

Figure 3.

The outward opening state of SGLT2 bound to the inhibitor captured by the author is quite different from the inward opening state of prokaryotic vSGLT

Figure 4.

In summary, the author analyzed the structure of the SGLT2-MAP17 complex and the inhibitor by cryo-electron microscopy, and found that the inhibitor locks SGLT2 in an open state, determined the binding site of the SGLT2 inhibitor, and explained the inhibitor's inhibition The working mechanism of SGLT2 (Figure 4) provides a structural basis for the further optimization of SGLT family inhibitors

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