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==Structure of BACE Bound to (R)-5-cyclopropyl-2-imino-3-methyl-5-(3-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)imidazolidin-4-one== | ==Structure of BACE Bound to (R)-5-cyclopropyl-2-imino-3-methyl-5-(3-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)imidazolidin-4-one== | ||
<StructureSection load='4djy' size='340' side='right' caption='[[4djy]], [[Resolution|resolution]] 1.86Å' scene=''> | <StructureSection load='4djy' size='340' side='right' caption='[[4djy]], [[Resolution|resolution]] 1.86Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4djy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[4djy]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DJY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DJY FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KR:(2E,5R)-5-CYCLOPROPYL-2-IMINO-3-METHYL-5-{3-[5-(PROP-1-YN-1-YL)PYRIDIN-3-YL]PHENYL}IMIDAZOLIDIN-4-ONE'>0KR</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0KR:(2E,5R)-5-CYCLOPROPYL-2-IMINO-3-METHYL-5-{3-[5-(PROP-1-YN-1-YL)PYRIDIN-3-YL]PHENYL}IMIDAZOLIDIN-4-ONE'>0KR</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dju|4dju]], [[4djv|4djv]], [[4djw|4djw]], [[4djx|4djx]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dju|4dju]], [[4djv|4djv]], [[4djw|4djw]], [[4djx|4djx]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE, BACE1, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE, BACE1, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='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=4djy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4djy RCSB], [http://www.ebi.ac.uk/pdbsum/4djy PDBsum]</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=4djy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djy OCA], [http://pdbe.org/4djy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4djy RCSB], [http://www.ebi.ac.uk/pdbsum/4djy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4djy ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4djy" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Human]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Cumming, J]] | [[Category: Cumming, J]] | ||
Revision as of 00:23, 5 August 2016
Structure of BACE Bound to (R)-5-cyclopropyl-2-imino-3-methyl-5-(3-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)imidazolidin-4-oneStructure of BACE Bound to (R)-5-cyclopropyl-2-imino-3-methyl-5-(3-(5-(prop-1-yn-1-yl)pyridin-3-yl)phenyl)imidazolidin-4-one
Structural highlights
Function[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.[1] [2] Publication Abstract from PubMedFrom an initial lead 1, a structure-based design approach led to identification of a novel, high-affinity iminohydantoin BACE1 inhibitor that lowers CNS-derived Abeta following oral administration to rats. Herein we report SAR development in the S3 and F' subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for the optimized compound. Structure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor.,Cumming JN, Smith EM, Wang L, Misiaszek J, Durkin J, Pan J, Iserloh U, Wu Y, Zhu Z, Strickland C, Voigt J, Chen X, Kennedy ME, Kuvelkar R, Hyde LA, Cox K, Favreau L, Czarniecki MF, Greenlee WJ, McKittrick BA, Parker EM, Stamford AW Bioorg Med Chem Lett. 2012 Apr 1;22(7):2444-9. Epub 2012 Feb 16. PMID:22390835[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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