2ohp: Difference between revisions
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==X-ray crystal structure of beta secretase complexed with compound 3== | ==X-ray crystal structure of beta secretase complexed with compound 3== | ||
<StructureSection load='2ohp' size='340' side='right' caption='[[2ohp]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='2ohp' size='340' side='right' caption='[[2ohp]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
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<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 HUMAN])</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 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=2ohp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohp OCA], [http://pdbe.org/2ohp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ohp RCSB], [http://www.ebi.ac.uk/pdbsum/2ohp 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=2ohp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohp OCA], [http://pdbe.org/2ohp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ohp RCSB], [http://www.ebi.ac.uk/pdbsum/2ohp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ohp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</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/ | </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=2ohp ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2ohp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2ohp" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Patel, S]] | [[Category: Patel, S]] | ||
[[Category: Alternative splicing]] | |||
[[Category: Alzheimer's disease]] | [[Category: Alzheimer's disease]] | ||
[[Category: Aspartic protease]] | [[Category: Aspartic protease]] | ||
Revision as of 12:01, 18 October 2017
X-ray crystal structure of beta secretase complexed with compound 3X-ray crystal structure of beta secretase complexed with compound 3
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 PubMedFragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM). Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase.,Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:17315857[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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