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[[Image:2viy.jpg|left|200px]]<br /><applet load="2viy" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2viy, resolution 1.82&Aring;" />
'''HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-(PENTYLSULFONYL)BENZAMIDE'''<br />


==Overview==
==Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(pentylsulfonyl)benzamide==
<StructureSection load='2viy' size='340' side='right'caption='[[2viy]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2viy]] 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=2VIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VIY FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VG3:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(PENTYLSULFONYL)BENZAMIDE'>VG3</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]], [[2vie|2vie]], [[2va6|2va6]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[1w51|1w51]], [[2viz|2viz]]</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=2viy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2viy OCA], [https://pdbe.org/2viy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2viy RCSB], [https://www.ebi.ac.uk/pdbsum/2viy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2viy 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/vi/2viy_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=2viy ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.
Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.


==About this Structure==
BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs).,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):1011-6. Epub 2007 Dec 15. PMID:18171614<ref>PMID:18171614</ref>
2VIY is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=VG3:'>VG3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Vg3+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIY OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs)., 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):1011-6. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18171614 18171614]
</div>
[[Category: Homo sapiens]]
<div class="pdbe-citations 2viy" 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: Memapsin 2]]
[[Category: Single protein]]
[[Category: Brien, A O]]
[[Category: Brien, A O.]]
[[Category: Clarke, B]]
[[Category: Clarke, B.]]
[[Category: Demont, E]]
[[Category: Demont, E.]]
[[Category: Dingwall, C]]
[[Category: Dingwall, C.]]
[[Category: Dunsdon, R]]
[[Category: Dunsdon, R.]]
[[Category: Faller, A]]
[[Category: Faller, A.]]
[[Category: Hawkins, J]]
[[Category: Hawkins, J.]]
[[Category: Hussain, I]]
[[Category: Hussain, I.]]
[[Category: MacPherson, D]]
[[Category: Macpherson, D.]]
[[Category: Maile, G]]
[[Category: Maile, G.]]
[[Category: Matico, R]]
[[Category: Matico, R.]]
[[Category: Milner, P]]
[[Category: Milner, P.]]
[[Category: Mosley, J]]
[[Category: Mosley, J.]]
[[Category: Naylor, A]]
[[Category: Naylor, A.]]
[[Category: Redshaw, S]]
[[Category: Redshaw, S.]]
[[Category: Riddell, D]]
[[Category: Riddell, D.]]
[[Category: Rowland, P]]
[[Category: Rowland, P.]]
[[Category: Smith, K]]
[[Category: Smith, K.]]
[[Category: Soleil, V]]
[[Category: Soleil, V.]]
[[Category: Stanway, S]]
[[Category: Stanway, S.]]
[[Category: Stemp, G]]
[[Category: Stemp, G.]]
[[Category: Sweitzer, S]]
[[Category: Sweitzer, S.]]
[[Category: Theobald, P]]
[[Category: Theobald, P.]]
[[Category: Vesey, D]]
[[Category: Vesey, D.]]
[[Category: Walter, D S]]
[[Category: Walter, D S.]]
[[Category: Ward, J]]
[[Category: Ward, J.]]
[[Category: Wayne, G]]
[[Category: Wayne, G.]]
[[Category: Alternative splicing]]
[[Category: VG3]]
[[Category: Asp-2]]
[[Category: alternative splicing]]
[[Category: Aspartyl protease]]
[[Category: asp-2]]
[[Category: Bace-1]]
[[Category: aspartyl protease]]
[[Category: Beta-secretase]]
[[Category: bace-1]]
[[Category: Beta-site app cleaving enzyme]]
[[Category: beta-secretase]]
[[Category: Glycoprotein]]
[[Category: beta-site app cleaving enzyme]]
[[Category: Hydrolase]]
[[Category: glycoprotein]]
[[Category: Memapsin-2]]
[[Category: hydrolase]]
[[Category: Membrane]]
[[Category: memapsin-2]]
[[Category: Protease]]
[[Category: membrane]]
[[Category: Transmembrane]]
[[Category: protease]]
[[Category: Zymogen]]
[[Category: transmembrane]]
[[Category: zymogen]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:56:18 2008''
Retrieved from "https://proteopedia.org/2viy"