2vkm: Difference between revisions

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{{Seed}}
[[Image:2vkm.jpg|left|200px]]


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==Crystal structure of GRL-8234 bound to BACE (Beta-secretase)==
The line below this paragraph, containing "STRUCTURE_2vkm", creates the "Structure Box" on the page.
<StructureSection load='2vkm' size='340' side='right'caption='[[2vkm]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<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>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</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>
{{STRUCTURE_2vkm|  PDB=2vkm  |  SCENE= }}
<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/initialview03.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.


===CRYSTAL STRUCTURE OF GRL-8234 BOUND TO BACE (BETA-SECRETASE)===
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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vkm" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_18180160}}, adds the Publication Abstract to the page
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 18180160 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_18180160}}
__TOC__
 
</StructureSection>
==About this Structure==
2VKM is a 4 chains structure of sequences 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=2VKM OCA].
 
==Reference==
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:[http://www.ncbi.nlm.nih.gov/pubmed/18180160 18180160]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Ghosh, A K.]]
[[Category: Large Structures]]
[[Category: Hong, L.]]
[[Category: Ghosh AK]]
[[Category: Tang, J.]]
[[Category: Hong L]]
[[Category: A-beta]]
[[Category: Tang J]]
[[Category: Alternative splicing]]
[[Category: Alzheimer]]
[[Category: App]]
[[Category: Aspartic protease]]
[[Category: Aspartyl protease]]
[[Category: Bace]]
[[Category: Beta secretase]]
[[Category: Drug design]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Memapsin]]
[[Category: Membrane]]
[[Category: Protease]]
[[Category: Transmembrane]]
[[Category: X- ray]]
[[Category: Zymogen]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 17 13:20:52 2008''
Retrieved from "https://proteopedia.org/2vkm"