6uj1 - Revision history

OCA at 07:52, 11 October 2023

OCA — Wed, 11 Oct 2023 07:52:29 GMT

←Older revision		Revision as of 07:52, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]], [[Resolution\|resolution]] 3.03Å' scene=''>		<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]], [[Resolution\|resolution]] 3.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6uj1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6uj1]] is a 2 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=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3M:(3S)-3-hydroxy-N-(2-methylpropyl)-N~2~-{[(4S)-17-[(methylsulfonyl)(propyl)amino]-2-oxo-3-azatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaen-4-yl]methyl}-L-norleucinamide'>L3M</scene~~></td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 3.03Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BACE2, AEPLC, ALP56, ASP21, CDA13, UNQ418/PRO852 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3M:(3S)-3-hydroxy-N-(2-methylpropyl)-N~2~-{[(4S)-17-[(methylsulfonyl)(propyl)amino]-2-oxo-3-azatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaen-4-yl]methyl}-L-norleucinamide'>L3M</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_1 Memapsin 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.45 3.4.23.45] </span></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=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [https://pdbe.org/6uj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></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=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [https://pdbe.org/6uj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/BACE2_HUMAN BACE2_HUMAN]] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672.<ref>PMID:10591213</ref> <ref>PMID:11083922</ref> <ref>PMID:15857888</ref> <ref>PMID:11423558</ref> <ref>PMID:16816112</ref>	+	[https://www.uniprot.org/uniprot/BACE2_HUMAN BACE2_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672.<ref>PMID:10591213</ref> <ref>PMID:11083922</ref> <ref>PMID:15857888</ref> <ref>PMID:11423558</ref> <ref>PMID:16816112</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6uj1" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6uj1" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta secretase 3D structures\|Beta secretase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Memapsin 1]]~~	+	[[Category: Ghosh AK]]
-	[[Category: Ghosh~~, A K~~]]	+	[[Category: Mesecar AD]]
-	[[Category: Mesecar~~, A D~~]]	+	[[Category: Yen YC]]
-	[[Category: Yen~~, Y C]]~~	+
-	~~[[Category: Aspartic protease]]~~	+
-	~~[[Category: Peptide binding protein~~]]	+

OCA at 08:28, 21 April 2021

OCA — Wed, 21 Apr 2021 08:28:17 GMT

←Older revision		Revision as of 08:28, 21 April 2021
Line 1:		Line 1:

	==BACE2 mutant in complex with a macrocyclic compound==		==BACE2 mutant in complex with a macrocyclic compound==
-	<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]]' scene=''>	+	<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]], [[Resolution\|resolution]] 3.03Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6uj1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>
-	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [~~http~~://pdbe.org/6uj1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=L3M:(3S)-3-hydroxy-N-(2-methylpropyl)-N~2~-{[(4S)-17-[(methylsulfonyl)(propyl)amino]-2-oxo-3-azatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaen-4-yl]methyl}-L-norleucinamide'>L3M</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BACE2, AEPLC, ALP56, ASP21, CDA13, UNQ418/PRO852 ([https://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'>[https://en.wikipedia.org/wiki/Memapsin_1 Memapsin 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.45 3.4.23.45] </span></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=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [https://pdbe.org/6uj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [https://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/BACE2_HUMAN BACE2_HUMAN]] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading 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. It has also been shown that it can cleave APP between residues 671 and 672.<ref>PMID:10591213</ref> <ref>PMID:11083922</ref> <ref>PMID:15857888</ref> <ref>PMID:11423558</ref> <ref>PMID:16816112</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The ability to perform routine structure-guided drug design for selective BACE inhibitors has been limited because of the lack of robust platform for BACE2 expression, purification, and crystallization. To overcome this limitation, we developed a platform that produces 2-3 mg of pure BACE2 protein per liter of E. coli culture, and we used this protein to design macrocyclic compounds that potently and selectively inhibit BACE1 over BACE2. Compound 2 was found to potently inhibit BACE 1 (Ki = 5 nM) with a selectivity of 214-fold over BACE2. The X-ray crystal structures of unbound BACE2 (2.2 A) and BACE2 bound to compound 3 (3.0 A and Ki = 7 nM) were determined and compared to the X-ray structures of BACE1 revealing the S1-S3 subsite as a selectivity determinant. This platform should enable a more rapid development of new and selective BACE inhibitors for the treatment of Alzheimer's disease or type II diabetes.
		+
		+	A Structure-Based Discovery Platform for BACE2 and the Development of Selective BACE Inhibitors.,Yen YC, Kammeyer AM, Tirlangi J, Ghosh AK, Mesecar AD ACS Chem Neurosci. 2021 Feb 17;12(4):581-588. doi: 10.1021/acschemneuro.0c00629. , Epub 2021 Feb 5. PMID:33544569<ref>PMID:33544569</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6uj1" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Ghosh AK]]	+	[[Category: Memapsin 1]]
-	[[Category: Mesecar AD]]	+	[[Category: Ghosh, A K]]
-	[[Category: Yen YC]]	+	[[Category: Mesecar, A D]]
		+	[[Category: Yen, Y C]]
		+	[[Category: Aspartic protease]]
		+	[[Category: Peptide binding protein]]

OCA at 06:17, 7 October 2020

OCA — Wed, 07 Oct 2020 06:17:50 GMT

←Older revision		Revision as of 06:17, 7 October 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6uj1 is ~~ON HOLD until Paper Publication~~	+	==BACE2 mutant in complex with a macrocyclic compound==
-		+	<StructureSection load='6uj1' size='340' side='right'caption='[[6uj1]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UJ1 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6UJ1 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6uj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uj1 OCA], [http://pdbe.org/6uj1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uj1 RCSB], [http://www.ebi.ac.uk/pdbsum/6uj1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uj1 ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Ghosh AK]]
		+	[[Category: Mesecar AD]]
		+	[[Category: Yen YC]]

OCA at 13:23, 29 January 2020

OCA — Wed, 29 Jan 2020 13:23:22 GMT

←Older revision		Revision as of 13:23, 29 January 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6uj1 is ON HOLD	+	The entry 6uj1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6uj1" [edit=sysop:move=sysop]

OCA — Thu, 10 Oct 2019 04:01:27 GMT

Protected "6uj1" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:01, 10 October 2019

OCA: New page: '''Unreleased structure''' The entry 6uj1 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Thu, 10 Oct 2019 04:01:26 GMT

New page: '''Unreleased structure''' The entry 6uj1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6uj1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]