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< | ==Structure of Beta-Secretase Complexed with Inhibitor== | ||
<StructureSection load='1fkn' size='340' side='right'caption='[[1fkn]], [[Resolution|resolution]] 1.90Å' 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]] 1.9Å</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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1fkn" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[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: | [[Category: Large Structures]] | ||
[[Category: Ghosh | [[Category: RCSB PDB Molecule of the Month]] | ||
[[Category: Hong | [[Category: Beta-Secretase]] | ||
[[Category: Koelsch | [[Category: Ghosh A]] | ||
[[Category: Lin | [[Category: Hong L]] | ||
[[Category: Tang | [[Category: Koelsch G]] | ||
[[Category: Terzyan | [[Category: Lin X]] | ||
[[Category: Wu | [[Category: Tang J]] | ||
[[Category: Zhang | [[Category: Terzyan S]] | ||
[[Category: Wu S]] | |||
[[Category: Zhang XC]] | |||
Latest revision as of 07:31, 17 October 2024
Structure of Beta-Secretase Complexed with InhibitorStructure of Beta-Secretase Complexed with Inhibitor
Structural highlights
FunctionBACE1_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.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMemapsin 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. 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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