View source for 3lhg


==Bace1 in complex with the aminohydantoin Compound 4g==
<StructureSection load='3lhg' size='340' side='right'caption='[[3lhg]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3lhg]] 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=3LHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LHG 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Z81:(5S)-2-AMINO-5-(2,5-DIFLUOROBIPHENYL-3-YL)-3-METHYL-5-PYRIDIN-4-YL-3,5-DIHYDRO-4H-IMIDAZOL-4-ONE'>Z81</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=3lhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lhg OCA], [https://pdbe.org/3lhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lhg RCSB], [https://www.ebi.ac.uk/pdbsum/3lhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lhg 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/lh/3lhg_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=3lhg ConSurf].
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== Publication Abstract from PubMed ==
A novel class of pyridinyl aminohydantoins was designed and prepared as highly potent BACE1 inhibitors. Compound (S)-4g showed excellent potency with IC(50) of 20 nM for BACE1. X-ray crystallography indicated that the interaction between pyridine nitrogen and the tryptophan Trp76 was a key feature in the S2' region of the enzyme that contributed to increased potency.

Pyridinyl aminohydantoins as small molecule BACE1 inhibitors.,Zhou P, Li Y, Fan Y, Wang Z, Chopra R, Olland A, Hu Y, Magolda RL, Pangalos M, Reinhart PH, Turner MJ, Bard J, Malamas MS, Robichaud AJ Bioorg Med Chem Lett. 2010 Apr 1;20(7):2326-9. Epub 2010 Feb 12. PMID:20202842<ref>PMID:20202842</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 3lhg" style="background-color:#fffaf0;"></div>

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