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3bug
From Proteopedia
(Difference between revisions)
(New page: 200px<br /><applet load="3bug" size="350" color="white" frame="true" align="right" spinBox="true" caption="3bug, resolution 2.50Å" /> '''BACE-1 complexed wit...) |
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| - | [[Image:3bug.jpg|left|200px]]<br /><applet load="3bug" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="3bug, resolution 2.50Å" /> | ||
| - | '''BACE-1 complexed with compound 3'''<br /> | ||
| - | == | + | ==BACE-1 complexed with compound 3== |
| + | <StructureSection load='3bug' size='340' side='right'caption='[[3bug]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3bug]] 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=3BUG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BUG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AEH:4-(2-AMINOETHYL)-2-ETHYLPHENOL'>AEH</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;'>[[3bra|3bra]], [[3buf|3buf]], [[3buh|3buh]]</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=3bug FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bug OCA], [https://pdbe.org/3bug PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bug RCSB], [https://www.ebi.ac.uk/pdbsum/3bug PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bug 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/bu/3bug_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=3bug ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads. | Fragment screening revealed that tyramine binds to the active site of the Alzheimer's disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads. | ||
| - | + | Tyramine fragment binding to BACE-1.,Kuglstatter A, Stahl M, Peters JU, Huber W, Stihle M, Schlatter D, Benz J, Ruf A, Roth D, Enderle T, Hennig M Bioorg Med Chem Lett. 2008 Feb 15;18(4):1304-7. Epub 2008 Jan 11. PMID:18226904<ref>PMID:18226904</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3bug" style="background-color:#fffaf0;"></div> | |
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| - | + | ==See Also== | |
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Human]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Memapsin 2]] | ||
| + | [[Category: Hennig, M]] | ||
| + | [[Category: Kuglstatter, A]] | ||
| + | [[Category: Alternative splicing]] | ||
| + | [[Category: Alzheimer's disease]] | ||
| + | [[Category: Aspartic protease]] | ||
| + | [[Category: Aspartyl protease]] | ||
| + | [[Category: Beta-secretase]] | ||
| + | [[Category: Fragment screen]] | ||
| + | [[Category: Glycoprotein]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Membrane]] | ||
| + | [[Category: Transmembrane]] | ||
| + | [[Category: Zymogen]] | ||
Current revision
BACE-1 complexed with compound 3
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