1fkn: Difference between revisions
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New page: left|200px<br /> <applet load="1fkn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1fkn, resolution 1.90Å" /> '''STRUCTURE OF BETA-S... |
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== | ==Structure of Beta-Secretase Complexed with Inhibitor== | ||
Memapsin 2 (beta-secretase) is a membrane-associated aspartic protease | <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 04:31, 17 October 2024
Structure of Beta-Secretase Complexed with Inhibitor
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