4i10
From Proteopedia
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| - | + | ==Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates== | |
| - | + | <StructureSection load='4i10' size='340' side='right' caption='[[4i10]], [[Resolution|resolution]] 2.07Å' scene=''> | |
| - | { | + | == Structural highlights == |
| + | <table><tr><td colspan='2'>[[4i10]] 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=4I10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I10 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BS:2-{(1S)-1-[(6-CHLORO-3,3-DIMETHYL-3,4-DIHYDROISOQUINOLIN-1-YL)AMINO]-2-PHENYLETHYL}PYRIDO[4,3-D]PYRIMIDIN-4(1H)-ONE'>1BS</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hzt|4hzt]], [[4i0z|4i0z]], [[4i11|4i11]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i10 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i10 RCSB], [http://www.ebi.ac.uk/pdbsum/4i10 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | <references | + | *[[Beta secretase|Beta secretase]] |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
| - | [[Category: Brecht, E | + | [[Category: Brecht, E]] |
| - | [[Category: Lougheed, J C | + | [[Category: Lougheed, J C]] |
| - | [[Category: Yao, N H | + | [[Category: Yao, N H]] |
[[Category: Aspartic protease]] | [[Category: Aspartic protease]] | ||
[[Category: Hydrolase-hydrolase inhibitor complex]] | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
Revision as of 12:35, 21 December 2014
Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates
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