8wby
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of ACE2-B0AT1 complex with JX98== | |
| + | <StructureSection load='8wby' size='340' side='right'caption='[[8wby]], [[Resolution|resolution]] 3.18Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8wby]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8WBY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8WBY FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.18Å</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8wby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8wby OCA], [https://pdbe.org/8wby PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8wby RCSB], [https://www.ebi.ac.uk/pdbsum/8wby PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8wby ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/S6A19_HUMAN S6A19_HUMAN] Hartnup disease;Iminoglycinuria. The disease is caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for hyperglycinuria. The disease may be caused by mutations affecting the gene represented in this entry. SLC6A19 deficiency combined with haploinsufficiency of SLC6A20 or partially inactivating mutations in SLC36A2, can be responsible for iminoglycinuria. Additional polymorphisms and mutations in SLC6A18 can contribute to the IG phenotype in some families. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/S6A19_HUMAN S6A19_HUMAN] Transporter that mediates resorption of neutral amino acids across the apical membrane of renal and intestinal epithelial cells (PubMed:18424768, PubMed:18484095, PubMed:19185582, PubMed:26240152). This uptake is sodium-dependent and chloride-independent (PubMed:19185582, PubMed:15286788). Requires CLTRN in kidney or ACE2 in intestine for cell surface expression and amino acid transporter activity (PubMed:19185582, PubMed:18424768).<ref>PMID:15286788</ref> <ref>PMID:18424768</ref> <ref>PMID:18484095</ref> <ref>PMID:19185582</ref> <ref>PMID:26240152</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The epithelial neutral amino acid transporter B(0)AT1 (SLC6A19) is the major transporter for the absorption of neutral amino acids in the intestine and their reabsorption in the kidney. Mouse models have demonstrated that lack of B(0)AT1 can normalize elevated plasma amino acids in rare disorders of amino acid metabolism such as phenylketonuria and urea-cycle disorders, implying a pharmacological approach for their treatment. Here we employ a medicinal chemistry approach to generate B(0)AT1 inhibitors with IC(50)-values of 31-90 nM. High-resolution cryo-EM structures of B(0)AT1 in the presence of two compounds from this series identified an allosteric binding site in the vestibule of the transporter. Mechanistically, binding of these inhibitors prevents a movement of TM1 and TM6 that is required for the transporter to make a conformational change from an outward open state to the occluded state. | ||
| - | + | Molecular basis of inhibition of the amino acid transporter B(0)AT1 (SLC6A19).,Xu J, Hu Z, Dai L, Yadav A, Jiang Y, Broer A, Gardiner MG, McLeod M, Yan R, Broer S Nat Commun. 2024 Aug 22;15(1):7224. doi: 10.1038/s41467-024-51748-1. PMID:39174516<ref>PMID:39174516</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8wby" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dai L]] | ||
| + | [[Category: Hu Z]] | ||
| + | [[Category: Yan R]] | ||
Current revision
Cryo-EM structure of ACE2-B0AT1 complex with JX98
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Categories: Homo sapiens | Large Structures | Dai L | Hu Z | Yan R
