2vj7

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[[Image:2vj7.jpg|left|200px]]
 
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{{Structure
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==Human BACE-1 in complex with 3-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-5-(2-oxo-1-pyrrolidinyl)benzamide==
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|PDB= 2vj7 |SIZE=350|CAPTION= <scene name='initialview01'>2vj7</scene>, resolution 1.60&Aring;
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<StructureSection load='2vj7' size='340' side='right'caption='[[2vj7]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Vg6+Binding+Site+For+Chain+A'>AC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=VG6:'>VG6</scene>
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<table><tr><td colspan='2'>[[2vj7]] 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=2VJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VJ7 FirstGlance]. <br>
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|ACTIVITY= [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]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VG6:N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)BENZYL]AMINO}PROPYL]-3-(ETHYLAMINO)-5-(2-OXOPYRROLIDIN-1-YL)BENZAMIDE'>VG6</scene></td></tr>
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}}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj7 OCA], [https://pdbe.org/2vj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vj7 RCSB], [https://www.ebi.ac.uk/pdbsum/2vj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vj7 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vj/2vj7_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2vj7 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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'''HUMAN BACE-1 IN COMPLEX WITH 3-(ETHYLAMINO)-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL) METHYL)AMINO)PROPYL)-5-(2-OXO-1-PYRROLIDINYL)BENZAMIDE'''
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2vj7" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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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.
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2VJ7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJ7 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/18166458 18166458]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Clarke B]]
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[[Category: Brien, A O.]]
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[[Category: Demont E]]
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[[Category: Clarke, B.]]
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[[Category: Dingwall C]]
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[[Category: Demont, E.]]
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[[Category: Dunsdon R]]
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[[Category: Dingwall, C.]]
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[[Category: Faller A]]
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[[Category: Dunsdon, R.]]
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[[Category: Hawkins J]]
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[[Category: Faller, A.]]
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[[Category: Hussain I]]
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[[Category: Hawkins, J.]]
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[[Category: MacPherson D]]
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[[Category: Hussain, I.]]
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[[Category: Maile G]]
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[[Category: Macpherson, D.]]
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[[Category: Matico R]]
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[[Category: Maile, G.]]
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[[Category: Milner P]]
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[[Category: Matico, R.]]
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[[Category: Mosley J]]
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[[Category: Milner, P.]]
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[[Category: Naylor A]]
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[[Category: Mosley, J.]]
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[[Category: O'Brien A]]
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[[Category: Naylor, A.]]
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[[Category: Redshaw S]]
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[[Category: Redshaw, S.]]
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[[Category: Riddell D]]
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[[Category: Riddell, D.]]
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[[Category: Rowland P]]
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[[Category: Rowland, P.]]
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[[Category: Smith K]]
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[[Category: Smith, K.]]
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[[Category: Soleil V]]
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[[Category: Soleil, V.]]
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[[Category: Stanway S]]
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[[Category: Stanway, S.]]
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[[Category: Stemp G]]
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[[Category: Stemp, G.]]
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[[Category: Sweitzer S]]
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[[Category: Sweitzer, S.]]
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[[Category: Theobald P]]
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[[Category: Theobald, P.]]
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[[Category: Vesey D]]
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[[Category: Vesey, D.]]
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[[Category: Walter DS]]
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[[Category: Walter, D S.]]
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[[Category: Ward J]]
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[[Category: Ward, J.]]
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[[Category: Wayne G]]
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[[Category: Wayne, G.]]
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[[Category: VG6]]
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[[Category: alternative splicing]]
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[[Category: asp-2]]
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[[Category: aspartyl protease]]
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[[Category: bace-1]]
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[[Category: beta-secretase]]
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[[Category: beta-site app cleaving enzyme]]
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[[Category: glycoprotein]]
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[[Category: hydrolase]]
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[[Category: memapsin-2]]
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[[Category: membrane]]
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[[Category: protease]]
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[[Category: transmembrane]]
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[[Category: zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:47:13 2008''
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Current revision

Human BACE-1 in complex with 3-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-5-(2-oxo-1-pyrrolidinyl)benzamide

PDB ID 2vj7

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