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2qu3
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 2qu3 is ON HOLD until Aug 03 2009 Authors: Chopra, R. Description: BACE1 with Compound 2 ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==BACE1 with Compound 2== | |
| + | <StructureSection load='2qu3' size='340' side='right'caption='[[2qu3]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2qu3]] is a 1 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=2QU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QU3 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=462:N-[AMINO(IMINO)METHYL]-2-[2-(2-CHLOROPHENYL)-4-(4-PROPOXYPHENYL)-3-THIENYL]ACETAMIDE'>462</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qu2|2qu2]]</div></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></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=2qu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qu3 OCA], [https://pdbe.org/2qu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qu3 RCSB], [https://www.ebi.ac.uk/pdbsum/2qu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qu3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN]] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qu/2qu3_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qu3 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of thiophene-substituted acylguanidines were designed from a pyrrole substituted acylguanidine HTS lead. This template allowed a greater flexibility, through differential Suzuki couplings, to explore the binding site of BACE1 and to enhance the inhibitory potencies. This exploration provided a 25-fold enhancement in potency to yield compound 10a, which was 150 nM in a BACE1 FRET assay. | ||
| - | + | Thiophene substituted acylguanidines as BACE1 inhibitors.,Fobare WF, Solvibile WR, Robichaud AJ, Malamas MS, Manas E, Turner J, Hu Y, Wagner E, Chopra R, Cowling R, Jin G, Bard J Bioorg Med Chem Lett. 2007 Oct 1;17(19):5353-6. Epub 2007 Aug 11. PMID:17761418<ref>PMID:17761418</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2qu3" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Memapsin 2]] | ||
| + | [[Category: Chopra, R]] | ||
| + | [[Category: Acylguanidine]] | ||
| + | [[Category: Alternative splicing]] | ||
| + | [[Category: Aspartyl protease]] | ||
| + | [[Category: Bace1]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Membrane]] | ||
| + | [[Category: Protease]] | ||
| + | [[Category: Transmembrane]] | ||
| + | [[Category: Zymogen]] | ||
Current revision
BACE1 with Compound 2
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