2ph6

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[[Image:2ph6.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure of Human Beta Secretase Complexed with inhibitor==
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|PDB= 2ph6 |SIZE=350|CAPTION= <scene name='initialview01'>2ph6</scene>, resolution 2.00&Aring;
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<StructureSection load='2ph6' size='340' side='right'caption='[[2ph6]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=712:3-({[(1R)-1-(4-FLUOROPHENYL)ETHYL]AMINO}CARBONYL)-5-[METHYL(METHYLSULFONYL)AMINO]BENZYL+ALPHA-METHYL-D-PHENYLALANINATE'>712</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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<table><tr><td colspan='2'>[[2ph6]] 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=2PH6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PH6 FirstGlance]. <br>
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|ACTIVITY= <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>
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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]] 2&#8491;</td></tr>
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|GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=712:3-({[(1R)-1-(4-FLUOROPHENYL)ETHYL]AMINO}CARBONYL)-5-[METHYL(METHYLSULFONYL)AMINO]BENZYL+ALPHA-METHYL-D-PHENYLALANINATE'>712</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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|DOMAIN=
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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=2ph6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ph6 OCA], [https://pdbe.org/2ph6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ph6 RCSB], [https://www.ebi.ac.uk/pdbsum/2ph6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ph6 ProSAT]</span></td></tr>
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|RELATEDENTRY=[[1tqf|1TQF]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ph6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ph6 OCA], [http://www.ebi.ac.uk/pdbsum/2ph6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ph6 RCSB]</span>
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== Function ==
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}}
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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/ph/2ph6_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=2ph6 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 Letter describes the design and synthesis of tertiary carbinamine macrocyclic inhibitors of the beta-secretase (BACE-1) enzyme. These macrocyclic inhibitors, some of which incorporate novel P2 substituents, display a 2- to 100-fold increase in potency relative to the previously described acyclic analogs while affording greater stability.
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'''Crystal Structure of Human Beta Secretase Complexed with inhibitor'''
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Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors.,Lindsley SR, Moore KP, Rajapakse HA, Selnick HG, Young MB, Zhu H, Munshi S, Kuo L, McGaughey GB, Colussi D, Crouthamel MC, Lai MT, Pietrak B, Price EA, Sankaranarayanan S, Simon AJ, Seabrook GR, Hazuda DJ, Pudvah NT, Hochman JH, Graham SL, Vacca JP, Nantermet PG Bioorg Med Chem Lett. 2007 Jul 15;17(14):4057-61. Epub 2007 Apr 27. PMID:17482814<ref>PMID:17482814</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 2ph6" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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This Letter describes the design and synthesis of tertiary carbinamine macrocyclic inhibitors of the beta-secretase (BACE-1) enzyme. These macrocyclic inhibitors, some of which incorporate novel P2 substituents, display a 2- to 100-fold increase in potency relative to the previously described acyclic analogs while affording greater stability.
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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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2PH6 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=2PH6 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Design, synthesis, and SAR of macrocyclic tertiary carbinamine BACE-1 inhibitors., Lindsley SR, Moore KP, Rajapakse HA, Selnick HG, Young MB, Zhu H, Munshi S, Kuo L, McGaughey GB, Colussi D, Crouthamel MC, Lai MT, Pietrak B, Price EA, Sankaranarayanan S, Simon AJ, Seabrook GR, Hazuda DJ, Pudvah NT, Hochman JH, Graham SL, Vacca JP, Nantermet PG, Bioorg Med Chem Lett. 2007 Jul 15;17(14):4057-61. Epub 2007 Apr 27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17482814 17482814]
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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: Munshi S]]
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[[Category: Munshi, S.]]
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[[Category: aspartyl protease]]
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[[Category: bace]]
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[[Category: hydrolase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:35:51 2008''
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Current revision

Crystal Structure of Human Beta Secretase Complexed with inhibitor

PDB ID 2ph6

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