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[[Image:1fkn.gif|left|200px]]
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{{STRUCTURE_1fkn|  PDB=1fkn  |  SCENE=  }}
'''STRUCTURE OF BETA-SECRETASE COMPLEXED WITH INHIBITOR'''


==Structure of Beta-Secretase Complexed with Inhibitor==
<StructureSection load='1fkn' size='340' side='right'caption='[[1fkn]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1fkn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The July 2006 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Amyloid-beta Precursor Protein''  by David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2006_7 10.2210/rcsb_pdb/mom_2006_7]. The July 2009 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''beta-Secretase''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2009_7 10.2210/rcsb_pdb/mom_2009_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1FKN 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OL:(2R,4S,5S)-5-AMINO-4-HYDROXY-2,7-DIMETHYLOCTANOIC+ACID'>1OL</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=1fkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1fkn OCA], [https://pdbe.org/1fkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1fkn RCSB], [https://www.ebi.ac.uk/pdbsum/1fkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1fkn 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/fk/1fkn_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=1fkn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.


==Overview==
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor.,Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC, Tang J Science. 2000 Oct 6;290(5489):150-3. PMID:11021803<ref>PMID:11021803</ref>
Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease involved in the production of beta-amyloid peptide in Alzheimer's disease and is a major target for drug design. We determined the crystal structure of the protease domain of human memapsin 2 complexed to an eight-residue inhibitor at 1.9 angstrom resolution. The active site of memapsin 2 is more open and less hydrophobic than that of other human aspartic proteases. The subsite locations from S4 to S2' are well defined. A kink of the inhibitor chain at P2' and the change of chain direction of P3' and P4' may be mimicked to provide inhibitor selectivity.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1FKN is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The following page contains interesting information on the relation of 1FKN with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb79_1.html Amyloid-beta Precursor Protein]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1FKN OCA].
</div>
<div class="pdbe-citations 1fkn" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Structure of the protease domain of memapsin 2 (beta-secretase) complexed with inhibitor., Hong L, Koelsch G, Lin X, Wu S, Terzyan S, Ghosh AK, Zhang XC, Tang J, Science. 2000 Oct 6;290(5489):150-3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11021803 11021803]
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Amyloid-beta Precursor Protein]]
[[Category: Amyloid-beta Precursor Protein]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Ghosh, A.]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Hong, L.]]
[[Category: Beta-Secretase]]
[[Category: Koelsch, G.]]
[[Category: Ghosh A]]
[[Category: Lin, X.]]
[[Category: Hong L]]
[[Category: Tang, J.]]
[[Category: Koelsch G]]
[[Category: Terzyan, S.]]
[[Category: Lin X]]
[[Category: Wu, S.]]
[[Category: Tang J]]
[[Category: Zhang, X C.]]
[[Category: Terzyan S]]
[[Category: Alzheimer's disease]]
[[Category: Wu S]]
[[Category: Aspartic protease]]
[[Category: Zhang XC]]
[[Category: Base]]
[[Category: Beta-secretase]]
[[Category: Memapsin 2]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 16:26:16 2008''
Retrieved from "https://proteopedia.org/1fkn"