2qmd: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2qmd]] is a 2 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=2QMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QMD FirstGlance]. <br> | <table><tr><td colspan='2'>[[2qmd]] is a 2 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=2QMD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QMD FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CS7:N-[(1S,2R)-2-[(2R,4R)-4-(BENZYLOXY)PYRROLIDIN-2-YL]-1-(3,5-DIFLUOROBENZYL)-2-HYDROXYETHYL]-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE'>CS7</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CS7:N-[(1S,2R)-2-[(2R,4R)-4-(BENZYLOXY)PYRROLIDIN-2-YL]-1-(3,5-DIFLUOROBENZYL)-2-HYDROXYETHYL]-5-METHYL-N,N-DIPROPYLISOPHTHALAMIDE'>CS7</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qk5|2qk5]], [[2qkj|2qkj]], [[2qmf|2qmf]], [[2qmg|2qmg]], [[2qp8|2qp8]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qk5|2qk5]], [[2qkj|2qkj]], [[2qmf|2qmf]], [[2qmg|2qmg]], [[2qp8|2qp8]]</td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | ||
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qmd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qmd RCSB], [http://www.ebi.ac.uk/pdbsum/2qmd 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=2qmd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qmd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2qmd RCSB], [http://www.ebi.ac.uk/pdbsum/2qmd PDBsum]</span></td></tr> | ||
<table> | </table> | ||
== Function == | |||
[[http://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 == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Iserloh, U | [[Category: Iserloh, U]] | ||
[[Category: Strickland, C O | [[Category: Strickland, C O]] | ||
[[Category: Aspartyl protease]] | [[Category: Aspartyl protease]] | ||
[[Category: Bace1]] | [[Category: Bace1]] | ||
Revision as of 23:41, 25 December 2014
Structure of BACE Bound to SCH722924Structure of BACE Bound to SCH722924
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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBased on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date. Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.,Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J Bioorg Med Chem Lett. 2008 Jan 1;18(1):414-7. Epub 2007 Nov 6. PMID:18023580[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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