4i11

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[[Image:4i11.jpg|left|200px]]
 
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{{STRUCTURE_4i11| PDB=4i11 | SCENE= }}
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==Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.==
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<StructureSection load='4i11' size='340' side='right'caption='[[4i11]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4i11]] 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=4I11 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I11 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]] 1.89&#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=1CH:N-(3,3-DIMETHYL-3,4-DIHYDROISOQUINOLIN-1-YL)-L-PHENYLALANINE'>1CH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4i11 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i11 OCA], [https://pdbe.org/4i11 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i11 RCSB], [https://www.ebi.ac.uk/pdbsum/4i11 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i11 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The structure-activity relationship of a series of dihydroisoquinoline BACE-1 inhibitors is described. Application of structure-based design to screening hit 1 yielded sub-micromolar inhibitors. Replacement of the carboxylic acid of 1 was guided by X-ray crystallography, which allowed the replacement of a key water-mediated hydrogen bond. This work culminated in compounds such as 31, which possess good BACE-1 potency, excellent permeability and a low P-gp efflux ratio.
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===Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.===
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Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.,Bowers S, Xu YZ, Yuan S, Probst GD, Hom RK, Chan W, Konradi AW, Sham HL, Zhu YL, Beroza P, Pan H, Brecht E, Yao N, Lougheed J, Tam D, Ren Z, Ruslim L, Bova MP, Artis DR Bioorg Med Chem Lett. 2013 Apr 1;23(7):2181-6. doi: 10.1016/j.bmcl.2013.01.103., Epub 2013 Feb 4. PMID:23465612<ref>PMID:23465612</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4i11" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[4i11]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I11 OCA].
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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>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
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[[Category: Large Structures]]
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[[Category: Artis, D R.]]
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[[Category: Artis DR]]
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[[Category: Beroza, P.]]
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[[Category: Beroza P]]
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[[Category: Bova, M.]]
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[[Category: Bova M]]
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[[Category: Bowers, B.]]
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[[Category: Bowers B]]
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[[Category: Brecht, E.]]
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[[Category: Brecht E]]
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[[Category: Chan, W.]]
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[[Category: Chan W]]
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[[Category: Hom, R K.]]
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[[Category: Hom RK]]
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[[Category: Konradi, A W.]]
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[[Category: Konradi AW]]
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[[Category: Lougheed, J.]]
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[[Category: Lougheed J]]
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[[Category: Pan, H.]]
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[[Category: Pan H]]
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[[Category: Probst, G D.]]
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[[Category: Probst GD]]
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[[Category: Sham, H L.]]
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[[Category: Sham HL]]
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[[Category: Tam, D.]]
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[[Category: Tam D]]
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[[Category: Xu, Y.]]
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[[Category: Xu Y]]
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[[Category: Yao, N.]]
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[[Category: Yao N]]
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[[Category: Yuan, S.]]
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[[Category: Yuan S]]
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[[Category: Zhu, Y L.]]
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[[Category: Zhu YL]]
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[[Category: Bace-1]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.

PDB ID 4i11

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