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==Crystal structure of Human Bace-1 bound to inhibitor== | |||
<StructureSection load='2ntr' size='340' side='right'caption='[[2ntr]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2ntr]] 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=2NTR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NTR 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L00:(2R)-2-(5-{3-CHLORO-6-((2-METHOXYETHYL){[(1S,2S)-2-METHYLCYCLOPROPYL]METHYL}AMINO)-2-[METHYL(METHYLSULFONYL)AMINO]PYRIDIN-4-YL}-1,3,4-OXADIAZOL-2-YL)-1-PHENYLPROPAN-2-AMINE'>L00</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=2ntr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ntr OCA], [https://pdbe.org/2ntr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ntr RCSB], [https://www.ebi.ac.uk/pdbsum/2ntr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ntr 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/nt/2ntr_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=2ntr ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in the S(3) pocket. These X-ray structures were used to correlate K(i) values, which span over five orders of magnitude, with the calculated interaction energy, using the Merck Molecular Force Field for a series of 19 tertiary carbinamine inhibitors. | |||
Beta-secretase (BACE-1) inhibitors: accounting for 10s loop flexibility using rigid active sites.,McGaughey GB, Colussi D, Graham SL, Lai MT, Munshi SK, Nantermet PG, Pietrak B, Rajapakse HA, Selnick HG, Stauffer SR, Holloway MK Bioorg Med Chem Lett. 2007 Feb 15;17(4):1117-21. Epub 2006 Nov 6. PMID:17112725<ref>PMID:17112725</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2ntr" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta secretase|Beta secretase]] | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Munshi | [[Category: Munshi S]] | ||
Latest revision as of 11:21, 30 October 2024
Crystal structure of Human Bace-1 bound to inhibitorCrystal structure of Human Bace-1 bound to inhibitor
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 PubMedBACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in the S(3) pocket. These X-ray structures were used to correlate K(i) values, which span over five orders of magnitude, with the calculated interaction energy, using the Merck Molecular Force Field for a series of 19 tertiary carbinamine inhibitors. Beta-secretase (BACE-1) inhibitors: accounting for 10s loop flexibility using rigid active sites.,McGaughey GB, Colussi D, Graham SL, Lai MT, Munshi SK, Nantermet PG, Pietrak B, Rajapakse HA, Selnick HG, Stauffer SR, Holloway MK Bioorg Med Chem Lett. 2007 Feb 15;17(4):1117-21. Epub 2006 Nov 6. PMID:17112725[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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