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3k5c
From Proteopedia
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| - | [[Image:3k5c.png|left|200px]] | ||
| - | { | + | ==Human BACE-1 complex with NB-216== |
| + | <StructureSection load='3k5c' size='340' side='right' caption='[[3k5c]], [[Resolution|resolution]] 2.12Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3k5c]] 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=3K5C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3K5C FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0BI:(4S)-4-[(1R)-1-HYDROXY-2-({1-[3-(1-METHYLETHYL)PHENYL]CYCLOPROPYL}AMINO)ETHYL]-19-(METHOXYMETHYL)-11-OXA-3,16-DIAZATRICYCLO[15.3.1.1~6,10~]DOCOSA-1(21),6(22),7,9,17,19-HEXAEN-2-ONE'>0BI</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3dv5|3dv5]], [[3k5d|3k5d]], [[3k5f|3k5f]], [[3k5g|3k5g]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE, BACE1, KIAA1149 ([http://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'>[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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3k5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k5c OCA], [http://pdbe.org/3k5c PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3k5c RCSB], [http://www.ebi.ac.uk/pdbsum/3k5c PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3k5c 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/k5/3k5c_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=3k5c ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of macrocyclic peptidic BACE-1 inhibitors was designed. While potency on BACE-1 was rather high, the first set of compounds showed poor brain permeation and high efflux in the MDRI-MDCK assay. The replacement of the secondary benzylamino group with a phenylcyclopropylamino group maintained potency on BACE-1, while P-glycoprotein-mediated efflux was significantly reduced and brain permeation improved. Several compounds from this series demonstrated acute reduction of Abeta in human APP-wildtype transgenic (APP51/16) mice after oral administration. | ||
| - | + | Macrocyclic BACE-1 inhibitors acutely reduce Abeta in brain after po application.,Lerchner A, Machauer R, Betschart C, Veenstra S, Rueeger H, McCarthy C, Tintelnot-Blomley M, Jaton AL, Rabe S, Desrayaud S, Enz A, Staufenbiel M, Paganetti P, Rondeau JM, Neumann U Bioorg Med Chem Lett. 2010 Jan 15;20(2):603-7. Epub 2009 Nov 22. PMID:19963375<ref>PMID:19963375</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3k5c" style="background-color:#fffaf0;"></div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | + | </StructureSection> | |
| - | + | [[Category: Human]] | |
| - | == | + | |
| - | < | + | |
| - | [[Category: | + | |
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| - | [[Category: Rondeau, J M | + | [[Category: Rondeau, J M]] |
[[Category: Alzheimer's disease]] | [[Category: Alzheimer's disease]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
Current revision
Human BACE-1 complex with NB-216
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