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2hiz
From Proteopedia
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| - | [[Image:2hiz.jpg|left|200px]]<br /><applet load="2hiz" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="2hiz, resolution 2.500Å" /> | ||
| - | '''Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor'''<br /> | ||
| - | == | + | ==Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor== |
| + | <StructureSection load='2hiz' size='340' side='right'caption='[[2hiz]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2hiz]] is a 3 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=2HIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HIZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LIJ:BENZYL+[(1S)-2-({(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}AMINO)-2-OXO-1-{[(1-PROPYLBUTYL)SULFONYL]METHYL}ETHYL]CARBAMATE'>LIJ</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2hiz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hiz OCA], [https://pdbe.org/2hiz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hiz RCSB], [https://www.ebi.ac.uk/pdbsum/2hiz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hiz 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/hi/2hiz_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=2hiz ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
We describe a novel series of potent inhibitors of human beta-secretase. These compounds possess the hydroxyethyl amine transition state isostere. A 2.5A crystal structure of inhibitor 32 bound to BACE is provided. | We describe a novel series of potent inhibitors of human beta-secretase. These compounds possess the hydroxyethyl amine transition state isostere. A 2.5A crystal structure of inhibitor 32 bound to BACE is provided. | ||
| - | + | Design of potent inhibitors of human beta-secretase. Part 1.,Freskos JN, Fobian YM, Benson TE, Bienkowski MJ, Brown DL, Emmons TL, Heintz R, Laborde A, McDonald JJ, Mischke BV, Molyneaux JM, Moon JB, Mullins PB, Bryan Prince D, Paddock DJ, Tomasselli AG, Winterrowd G Bioorg Med Chem Lett. 2007 Jan 1;17(1):73-7. Epub 2006 Oct 4. PMID:17046251<ref>PMID:17046251</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2hiz" 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: Benson, T E]] | ||
| + | [[Category: Emmons, T L]] | ||
| + | [[Category: Paddock, D J]] | ||
| + | [[Category: Prince, D B]] | ||
| + | [[Category: Tomasselli, A G]] | ||
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Protein-inhibitor complex]] | ||
Current revision
Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor
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