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2qmf
From Proteopedia
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| - | [[Image:2qmf.jpg|left|200px]] | ||
| - | + | ==Structure of BACE Bound to SCH735310== | |
| - | + | <StructureSection load='2qmf' size='340' side='right'caption='[[2qmf]], [[Resolution|resolution]] 1.75Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[2qmf]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QMF FirstGlance]. <br> | |
| - | | | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CS9:N-{(1S,2R)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R,4R)-4-PHENOXYPYRROLIDIN-2-YL]ETHYL}-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE'>CS9</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</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;'>[[2qk5|2qk5]], [[2qkj|2qkj]], [[2qmd|2qmd]], [[2qmg|2qmg]], [[2qp8|2qp8]]</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 HUMAN])</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=2qmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qmf OCA], [https://pdbe.org/2qmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qmf RCSB], [https://www.ebi.ac.uk/pdbsum/2qmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qmf 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/qm/2qmf_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=2qmf ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. | ||
| - | + | Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.,Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580<ref>PMID:18023580</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 2qmf" style="background-color:#fffaf0;"></div> | ||
| - | == | + | ==See Also== |
| - | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Human]] |
| - | + | [[Category: Large Structures]] | |
| - | [[Category: | + | |
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| - | + | [[Category: Iserloh, U]] | |
| - | [[Category: Iserloh, U | + | [[Category: Strickland, C O]] |
| - | [[Category: Strickland, C O | + | [[Category: Alternative splicing]] |
| - | [[Category: | + | [[Category: Aspartyl protease]] |
| - | [[Category: | + | [[Category: Bace1]] |
| - | [[Category: | + | [[Category: Glycoprotein]] |
| - | [[Category: | + | [[Category: Hydrolase]] |
| - | [[Category: | + | [[Category: Membrane]] |
| - | [[Category: | + | [[Category: Protease]] |
| - | [[Category: | + | [[Category: Transmembrane]] |
| - | [[Category: | + | [[Category: Zymogen]] |
| - | [[Category: | + | |
| - | + | ||
| - | + | ||
Current revision
Structure of BACE Bound to SCH735310
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