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3dm6
From Proteopedia
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| - | [[Image:3dm6.png|left|200px]] | ||
| - | + | ==Beta-secretase 1 complexed with statine-based inhibitor== | |
| + | <StructureSection load='3dm6' size='340' side='right'caption='[[3dm6]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3dm6]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DM6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3DM6 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=757:5-[[(2S)-2-[[(3R,4S)-5-(3,5-difluorophenoxy)-3-hydroxy-4-[[3-(methyl-methylsulfonyl-amino)-5-[[(1R)-1-phenylethyl]carbamoyl]phenyl]carbonylamino]pentanoyl]amino]-3-methyl-butanoyl]amino]benzene-1,3-dicarboxylic+acid'>757</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://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'>[http://proteopedia.org/fgij/fg.htm?mol=3dm6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dm6 OCA], [http://pdbe.org/3dm6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3dm6 RCSB], [http://www.ebi.ac.uk/pdbsum/3dm6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3dm6 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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/dm/3dm6_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=3dm6 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modification introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors. | ||
| - | + | Design, synthesis and SAR of potent statine-based BACE-1 inhibitors: exploration of P1 phenoxy and benzyloxy residues.,Back M, Nyhlen J, Kvarnstrom I, Appelgren S, Borkakoti N, Jansson K, Lindberg J, Nystrom S, Hallberg A, Rosenquist S, Samuelsson B Bioorg Med Chem. 2008 Nov 1;16(21):9471-86. Epub 2008 Sep 19. PMID:18842420<ref>PMID:18842420</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3dm6" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Beta secretase|Beta secretase]] | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| - | [[Category: Borkakoti, N | + | [[Category: Borkakoti, N]] |
| - | [[Category: Lindberg, J | + | [[Category: Lindberg, J]] |
| - | [[Category: Nystrom, S | + | [[Category: Nystrom, S]] |
| + | [[Category: Alternative splicing]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
[[Category: Bace]] | [[Category: Bace]] | ||
Current revision
Beta-secretase 1 complexed with statine-based inhibitor
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Categories: Human | Large Structures | Memapsin 2 | Borkakoti, N | Lindberg, J | Nystrom, S | Alternative splicing | Aspartyl protease | Bace | Beta-secretase | Glycoprotein | Hydrolase | Inhibitor | Membrane | Protease | Statine | Transmembrane | Zymogen
