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2vkm
From Proteopedia
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| - | [[Image:2vkm.png|left|200px]] | ||
| - | + | ==Crystal structure of GRL-8234 bound to BACE (Beta-secretase)== | |
| + | <StructureSection load='2vkm' size='340' side='right'caption='[[2vkm]], [[Resolution|resolution]] 2.05Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2vkm]] is a 4 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=2VKM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VKM FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BSD:N-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>BSD</scene></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=2vkm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vkm OCA], [https://pdbe.org/2vkm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vkm RCSB], [https://www.ebi.ac.uk/pdbsum/2vkm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vkm 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/vk/2vkm_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=2vkm ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic beta-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K(i) 1.8 nM) and cellular (IC(50)=1 nM in Chinese hamster ovary cells) assays. Inhibitor 24 has also shown very impressive in vivo properties (up to 65% reduction of plasma A beta) in transgenic mice. The X-ray structure of protein-ligand complex of memapsin 2 revealed critical interactions in the memapsin 2 active site. | ||
| - | + | Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluation.,Ghosh AK, Kumaragurubaran N, Hong L, Kulkarni S, Xu X, Miller HB, Reddy DS, Weerasena V, Turner R, Chang W, Koelsch G, Tang J Bioorg Med Chem Lett. 2008 Feb 1;18(3):1031-6. Epub 2008 Jan 3. PMID:18180160<ref>PMID:18180160</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2vkm" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
| - | *[[Beta secretase|Beta secretase]] | + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Ghosh AK]] |
| - | [[Category: | + | [[Category: Hong L]] |
| - | [[Category: | + | [[Category: Tang J]] |
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Current revision
Crystal structure of GRL-8234 bound to BACE (Beta-secretase)
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