View source for 3lpi


==Structure of BACE Bound to SCH745132==
<StructureSection load='3lpi' size='340' side='right'caption='[[3lpi]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3lpi]] is a 2 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=3LPI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LPI 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene>, <scene name='pdbligand=Z74:N-{(1S,2S)-1-(3,5-DIFLUOROBENZYL)-2-HYDROXY-2-[(2R)-4-(PHENYLSULFONYL)PIPERAZIN-2-YL]ETHYL}-5-METHYL-N,N-DIPROPYLBENZENE-1,3-DICARBOXAMIDE'>Z74</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=3lpi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lpi OCA], [https://pdbe.org/3lpi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lpi RCSB], [https://www.ebi.ac.uk/pdbsum/3lpi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lpi 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/lp/3lpi_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=3lpi ConSurf].
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== Publication Abstract from PubMed ==
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Abeta(40) in transgenic mice with a single subcutaneous dose.

Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization.,Cumming J, Babu S, Huang Y, Carrol C, Chen X, Favreau L, Greenlee W, Guo T, Kennedy M, Kuvelkar R, Le T, Li G, McHugh N, Orth P, Ozgur L, Parker E, Saionz K, Stamford A, Strickland C, Tadesse D, Voigt J, Zhang L, Zhang Q Bioorg Med Chem Lett. 2010 May 1;20(9):2837-42. Epub 2010 Mar 12. PMID:20347593<ref>PMID:20347593</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 3lpi" 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: Cumming J]]
[[Category: Strickland C]]