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2g94

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(New page: 200px<br /> <applet load="2g94" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g94, resolution 1.86&Aring;" /> '''Crystal structure o...)
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[[Image:2g94.gif|left|200px]]<br />
 
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<applet load="2g94" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2g94, resolution 1.86&Aring;" />
 
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'''Crystal structure of beta-secretase bound to a potent and highly selective inhibitor.'''<br />
 
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==Overview==
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==Crystal structure of beta-secretase bound to a potent and highly selective inhibitor.==
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<StructureSection load='2g94' size='340' side='right'caption='[[2g94]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2g94]] is a 4 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=2G94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G94 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.86&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZPQ:N~2~-[(2R,4S,5S)-5-{[N-{[(3,5-DIMETHYL-1H-PYRAZOL-1-YL)METHOXY]CARBONYL}-3-(METHYLSULFONYL)-L-ALANYL]AMINO}-4-HYDROXY-2,7-DIMETHYLOCTANOYL]-N-ISOBUTYL-L-VALINAMIDE'>ZPQ</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2g94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g94 OCA], [https://pdbe.org/2g94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g94 RCSB], [https://www.ebi.ac.uk/pdbsum/2g94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g94 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g9/2g94_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2g94 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent inhibitory activity against memapsin 2 and selectivity over memapsin 1 (&gt;3800-fold) and cathepsin D (&gt;2500-fold). A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D.
Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent inhibitory activity against memapsin 2 and selectivity over memapsin 1 (&gt;3800-fold) and cathepsin D (&gt;2500-fold). A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D.
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==About this Structure==
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Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors.,Ghosh AK, Kumaragurubaran N, Hong L, Lei H, Hussain KA, Liu CF, Devasamudram T, Weerasena V, Turner R, Koelsch G, Bilcer G, Tang J J Am Chem Soc. 2006 Apr 26;128(16):5310-1. PMID:16620080<ref>PMID:16620080</ref>
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2G94 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZPQ as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2G94 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors., Ghosh AK, Kumaragurubaran N, Hong L, Lei H, Hussain KA, Liu CF, Devasamudram T, Weerasena V, Turner R, Koelsch G, Bilcer G, Tang J, J Am Chem Soc. 2006 Apr 26;128(16):5310-1. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16620080 16620080]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2g94" style="background-color:#fffaf0;"></div>
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[[Category: Memapsin 2]]
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[[Category: Single protein]]
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[[Category: Ghosh, A.]]
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[[Category: Hong, L.]]
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[[Category: Tang, J.]]
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[[Category: ZPQ]]
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[[Category: alzheimer's disease]]
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[[Category: asp2]]
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[[Category: aspartic protease]]
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[[Category: bace]]
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[[Category: beta secretase]]
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[[Category: drug design]]
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[[Category: memapsin]]
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[[Category: protease inhibitor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:16:14 2007''
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==See Also==
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ghosh A]]
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[[Category: Hong L]]
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[[Category: Tang J]]

Current revision

Crystal structure of beta-secretase bound to a potent and highly selective inhibitor.

PDB ID 2g94

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