View source for 2qzl


==Crystal Structure of human Beta Secretase complexed with IXS==
<StructureSection load='2qzl' size='340' side='right'caption='[[2qzl]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2qzl]] 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=2QZL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QZL 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IXS:N-[(1S)-1-BENZYL-2-{[(1S)-2-(ISOBUTYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}ETHYL]-N-[(1R)-1-(4-FLUOROPHENYL)ETHYL]-5-[METHYL(METHYLSULFONYL)AMINO]ISOPHTHALAMIDE'>IXS</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=2qzl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qzl OCA], [https://pdbe.org/2qzl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qzl RCSB], [https://www.ebi.ac.uk/pdbsum/2qzl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qzl 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/qz/2qzl_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=2qzl ConSurf].
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== Publication Abstract from PubMed ==
A series of beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing a psi(CH2NH) reduced amide bond were synthesized. Incorporation of this reduced amide isostere as a non-cleavable peptide surrogate afforded inhibitors possessing low nanomolar potencies in both an enzymatic and cell-based assay.

BACE-1 inhibition by a series of psi[CH2NH] reduced amide isosteres.,Coburn CA, Stachel SJ, Jones KG, Steele TG, Rush DM, DiMuzio J, Pietrak BL, Lai MT, Huang Q, Lineberger J, Jin L, Munshi S, Katharine Holloway M, Espeseth A, Simon A, Hazuda D, Graham SL, Vacca JP Bioorg Med Chem Lett. 2006 Jul 15;16(14):3635-8. Epub 2006 May 11. PMID:16690314<ref>PMID:16690314</ref>

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

==See Also==
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Munshi S]]