View source for 2vj6


==Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide==
<StructureSection load='2vj6' size='340' side='right'caption='[[2vj6]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vj6]] is a 1 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=2VJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VJ6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VG5:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(ETHYLAMINO)-5-(2-OXOPYRROLIDIN-1-YL)BENZAMIDE'>VG5</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;'>[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[2b8v|2b8v]], [[1ujk|1ujk]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[1w51|1w51]], [[2vj7|2vj7]]</div></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=2vj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj6 OCA], [https://pdbe.org/2vj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vj6 RCSB], [https://www.ebi.ac.uk/pdbsum/2vj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vj6 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/vj/2vj6_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=2vj6 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.

BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character.,Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G Bioorg Med Chem Lett. 2008 Feb 1;18(3):1017-21. Epub 2007 Dec 15. PMID:18166458<ref>PMID:18166458</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vj6" 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: Memapsin 2]]
[[Category: Brien, A O]]
[[Category: Clarke, B]]
[[Category: Demont, E]]
[[Category: Dingwall, C]]
[[Category: Dunsdon, R]]
[[Category: Faller, A]]
[[Category: Hawkins, J]]
[[Category: Hussain, I]]
[[Category: MacPherson, D]]
[[Category: Maile, G]]
[[Category: Matico, R]]
[[Category: Milner, P]]
[[Category: Mosley, J]]
[[Category: Naylor, A]]
[[Category: Redshaw, S]]
[[Category: Riddell, D]]
[[Category: Rowland, P]]
[[Category: Smith, K]]
[[Category: Soleil, V]]
[[Category: Stanway, S]]
[[Category: Stemp, G]]
[[Category: Sweitzer, S]]
[[Category: Theobald, P]]
[[Category: Vesey, D]]
[[Category: Walter, D S]]
[[Category: Ward, J]]
[[Category: Wayne, G]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Memapsin-2]]
[[Category: Membrane]]