8hdh
From Proteopedia
(Difference between revisions)
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[https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Familial renal glucosuria. The disease is caused by variants affecting the gene represented in this entry. | [https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Familial renal glucosuria. The disease is caused by variants affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Electrogenic Na(+)-coupled sugar | + | [https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).[UniProtKB:Q923I7]<ref>PMID:20980548</ref> <ref>PMID:28592437</ref> <ref>PMID:34880493</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sodium-glucose cotransporter 2 (SGLT2) is imporant in glucose reabsorption. SGLT2 inhibitors suppress renal glucose reabsorption, therefore reducing blood glucose levels in patients with type 2 diabetes. We and others have developed several SGLT2 inhibitors starting from phlorizin, a natural product. Using cryo-electron microscopy, we present the structures of human (h)SGLT2-MAP17 complexed with five natural or synthetic inhibitors. The four synthetic inhibitors (including canagliflozin) bind the transporter in the outward conformations, while phlorizin binds it in the inward conformation. The phlorizin-hSGLT2 interaction exhibits biphasic kinetics, suggesting that phlorizin alternately binds to the extracellular and intracellular sides. The Na(+)-bound outward-facing and unbound inward-open structures of hSGLT2-MAP17 suggest that the MAP17-associated bundle domain functions as a scaffold, with the hash domain rotating around the Na(+)-binding site. Thus, Na(+) binding stabilizes the outward-facing conformation, and its release promotes state transition to inward-open conformation, exhibiting a role of Na(+) in symport mechanism. These results provide structural evidence for the Na(+)-coupled alternating-access mechanism proposed for the transporter family. | ||
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| + | Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter.,Hiraizumi M, Akashi T, Murasaki K, Kishida H, Kumanomidou T, Torimoto N, Nureki O, Miyaguchi I Nat Struct Mol Biol. 2024 Jan;31(1):159-169. doi: 10.1038/s41594-023-01134-0. , Epub 2023 Dec 6. PMID:38057552<ref>PMID:38057552</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8hdh" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Sodium/glucose cotransporter 3D structures|Sodium/glucose cotransporter 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Hiraizumi M]] |
| - | [[Category: | + | [[Category: Kishida H]] |
| - | [[Category: | + | [[Category: Miyaguchi I]] |
| - | [[Category: | + | [[Category: Nureki O]] |
Current revision
Structure of human SGLT2-MAP17 complex with Canagliflozin
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