2b8l: Difference between revisions

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[[Image:2b8l.gif|left|200px]]


{{Structure
==Crystal structure of human beta secretase complexed with inhibitor==
|PDB= 2b8l |SIZE=350|CAPTION= <scene name='initialview01'>2b8l</scene>, resolution 1.7&Aring;
<StructureSection load='2b8l' size='340' side='right'caption='[[2b8l]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=5HA:N-[(1S,2R)-1-BENZYL-3-(CYCLOPROPYLAMINO)-2-HYDROXYPROPYL]-5-[METHYL(METHYLSULFONYL)AMINO]-N&#39;-[(1R)-1-PHENYLETHYL]ISOPHTHALAMIDE'>5HA</scene>
<table><tr><td colspan='2'>[[2b8l]] 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=2B8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B8L FirstGlance]. <br>
|ACTIVITY= [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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</td></tr>
|GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5HA:N-[(1S,2R)-1-BENZYL-3-(CYCLOPROPYLAMINO)-2-HYDROXYPROPYL]-5-[METHYL(METHYLSULFONYL)AMINO]-N-[(1R)-1-PHENYLETHYL]ISOPHTHALAMIDE'>5HA</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=2b8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b8l OCA], [https://pdbe.org/2b8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b8l RCSB], [https://www.ebi.ac.uk/pdbsum/2b8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b8l 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/b8/2b8l_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=2b8l ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.


'''Crystal structure of human beta secretase complexed with inhibitor'''
Conformationally biased P3 amide replacements of beta-secretase inhibitors.,Stachel SJ, Coburn CA, Steele TG, Crouthamel MC, Pietrak BL, Lai MT, Holloway MK, Munshi SK, Graham SL, Vacca JP Bioorg Med Chem Lett. 2006 Feb;16(3):641-4. Epub 2005 Nov 2. PMID:16263281<ref>PMID:16263281</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2b8l" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
 
== References ==
==About this Structure==
<references/>
2B8L 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=2B8L OCA].
__TOC__
 
</StructureSection>
==Reference==
Conformationally biased P3 amide replacements of beta-secretase inhibitors., Stachel SJ, Coburn CA, Steele TG, Crouthamel MC, Pietrak BL, Lai MT, Holloway MK, Munshi SK, Graham SL, Vacca JP, Bioorg Med Chem Lett. 2006 Feb;16(3):641-4. Epub 2005 Nov 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16263281 16263281]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Memapsin 2]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Kuo L]]
[[Category: Kuo, L.]]
[[Category: Munshi SK]]
[[Category: Munshi, S K.]]
[[Category: 5HA]]
[[Category: aspartyl protease]]
[[Category: bace]]
[[Category: hydrolase]]
 
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Retrieved from "https://proteopedia.org/2b8l"