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7y5z
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7y5z is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==CryoEM structure of human PS2-containing gamma-secretase== |
| + | <StructureSection load='7y5z' size='340' side='right'caption='[[7y5z]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7y5z]] 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=7Y5Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5Z FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PC1:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PC1</scene></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=7y5z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5z OCA], [https://pdbe.org/7y5z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5z RCSB], [https://www.ebi.ac.uk/pdbsum/7y5z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5z ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN] Hidradenitis suppurativa. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NICA_HUMAN NICA_HUMAN] Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor required for the assembly of the gamma-secretase complex. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inhibition of gamma-secretase activity represents a potential therapeutic strategy for Alzheimer's disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of gamma-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing gamma-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 A. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting gamma-secretase. | ||
| - | + | Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560.,Guo X, Wang Y, Zhou J, Jin C, Wang J, Jia B, Jing D, Yan C, Lei J, Zhou R, Shi Y Nat Commun. 2022 Oct 22;13(1):6299. doi: 10.1038/s41467-022-33817-5. PMID:36272978<ref>PMID:36272978</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7y5z" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Guo X]] | ||
| + | [[Category: Jia B]] | ||
| + | [[Category: Jin C]] | ||
| + | [[Category: Jing D]] | ||
| + | [[Category: Lei J]] | ||
| + | [[Category: Shi Y]] | ||
| + | [[Category: Wang J]] | ||
| + | [[Category: Wang Y]] | ||
| + | [[Category: Yan C]] | ||
| + | [[Category: Zhou J]] | ||
| + | [[Category: Zhou R]] | ||
Current revision
CryoEM structure of human PS2-containing gamma-secretase
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Categories: Homo sapiens | Large Structures | Guo X | Jia B | Jin C | Jing D | Lei J | Shi Y | Wang J | Wang Y | Yan C | Zhou J | Zhou R
