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==Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor (2)== | |||
<StructureSection load='2hm1' size='340' side='right'caption='[[2hm1]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2hm1]] 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=2HM1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HM1 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LIQ:N-{(1S)-2-({(1S,2R)-1-(3,5-DIFLUOROBENZYL)-3-[(3-ETHYLBENZYL)AMINO]-2-HYDROXYPROPYL}AMINO)-2-OXO-1-[(PENTYLSULFONYL)METHYL]ETHYL}NICOTINAMIDE'>LIQ</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2hm1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hm1 OCA], [https://pdbe.org/2hm1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hm1 RCSB], [https://www.ebi.ac.uk/pdbsum/2hm1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hm1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hm/2hm1_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=2hm1 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown. | |||
Design of potent inhibitors of human beta-secretase. Part 2.,Freskos JN, Fobian YM, Benson TE, Moon JB, Bienkowski MJ, Brown DL, Emmons TL, Heintz R, Laborde A, McDonald JJ, Mischke BV, Molyneaux JM, Mullins PB, Bryan Prince D, Paddock DJ, Tomasselli AG, Winterrowd G Bioorg Med Chem Lett. 2007 Jan 1;17(1):78-81. Epub 2006 Oct 4. PMID:17049233<ref>PMID:17049233</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2hm1" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Beta secretase 3D structures|Beta secretase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Benson TE]] | |||
[[Category: Benson | [[Category: Emmons TL]] | ||
[[Category: Emmons | [[Category: Paddock DJ]] | ||
[[Category: Paddock | [[Category: Prince DB]] | ||
[[Category: Prince | [[Category: Tomasselli AG]] | ||
[[Category: Tomasselli | |||
Latest revision as of 11:08, 30 October 2024
Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor (2)Crystal Structure of human beta-secretase (BACE) in the presence of an inhibitor (2)
Structural highlights
FunctionBACE1_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 PubMedWe describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown. Design of potent inhibitors of human beta-secretase. Part 2.,Freskos JN, Fobian YM, Benson TE, Moon JB, Bienkowski MJ, Brown DL, Emmons TL, Heintz R, Laborde A, McDonald JJ, Mischke BV, Molyneaux JM, Mullins PB, Bryan Prince D, Paddock DJ, Tomasselli AG, Winterrowd G Bioorg Med Chem Lett. 2007 Jan 1;17(1):78-81. Epub 2006 Oct 4. PMID:17049233[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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