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2b8l
From Proteopedia
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| - | [[Image:2b8l.gif|left|200px]]<br /><applet load="2b8l" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2b8l, resolution 1.7Å" /> | ||
| - | '''Crystal structure of human beta secretase complexed with inhibitor'''<br /> | ||
| - | == | + | ==Crystal structure of human beta secretase complexed with inhibitor== |
| + | <StructureSection load='2b8l' size='340' side='right'caption='[[2b8l]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2b8l]] 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=2B8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B8L FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5HA:N-[(1S,2R)-1-BENZYL-3-(CYCLOPROPYLAMINO)-2-HYDROXYPROPYL]-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]ISOPHTHALAMIDE'>5HA</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=2b8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b8l OCA], [https://pdbe.org/2b8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b8l RCSB], [https://www.ebi.ac.uk/pdbsum/2b8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b8l 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/b8/2b8l_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=2b8l ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described. | We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described. | ||
| - | + | Conformationally biased P3 amide replacements of beta-secretase inhibitors.,Stachel SJ, Coburn CA, Steele TG, Crouthamel MC, Pietrak BL, Lai MT, Holloway MK, Munshi SK, Graham SL, Vacca JP Bioorg Med Chem Lett. 2006 Feb;16(3):641-4. Epub 2005 Nov 2. PMID:16263281<ref>PMID:16263281</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2b8l" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Kuo L]] | ||
| + | [[Category: Munshi SK]] | ||
Current revision
Crystal structure of human beta secretase complexed with inhibitor
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