6nv7 - Revision history

OCA at 07:00, 11 October 2023

OCA — Wed, 11 Oct 2023 07:00:17 GMT

←Older revision		Revision as of 07:00, 11 October 2023
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	<StructureSection load='6nv7' size='340' side='right'caption='[[6nv7]], [[Resolution\|resolution]] 2.13Å' scene=''>		<StructureSection load='6nv7' size='340' side='right'caption='[[6nv7]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nv7]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NV7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6NV7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nv7]] is a 3 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=6NV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NV7 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L3J:(E)-N-(2-methylpropylidene)-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}-D-threoninamide'>L3J</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]] 2.132Å</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://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=L3J:(E)-N-(2-methylpropylidene)-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}-D-threoninamide'>L3J</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=6nv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nv7 OCA], [https://pdbe.org/6nv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nv7 RCSB], [https://www.ebi.ac.uk/pdbsum/6nv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nv7 ProSAT]</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=6nv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nv7 OCA], [~~http~~://pdbe.org/6nv7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6nv7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6nv7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6nv7 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== 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>	+	[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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	</div>		</div>
	<div class="pdbe-citations 6nv7" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6nv7" 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 2]]~~	+	[[Category: Ghosh AK]]
-	[[Category: Ghosh~~, A K~~]]	+	[[Category: Mesecar AD]]
-	[[Category: Mesecar~~, A D~~]]	+	[[Category: Yen YC]]
-	[[Category: Yen~~, Y C]]~~	+
-	~~[[Category: Inhibitor complex]]~~	+
-	~~[[Category: Peptide binding protein]]~~	+
-	~~[[Category: Peptide binding protein-inhibitor complex]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 17:37, 20 November 2019

OCA — Wed, 20 Nov 2019 17:37:57 GMT

←Older revision		Revision as of 17:37, 20 November 2019
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	<StructureSection load='6nv7' size='340' side='right'caption='[[6nv7]], [[Resolution\|resolution]] 2.13Å' scene=''>		<StructureSection load='6nv7' size='340' side='right'caption='[[6nv7]], [[Resolution\|resolution]] 2.13Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6nv7]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NV7 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6nv7]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NV7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L3J:(E)-N-(2-methylpropylidene)-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}-D-threoninamide'>L3J</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L3J:(E)-N-(2-methylpropylidene)-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}-D-threoninamide'>L3J</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([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=6nv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nv7 OCA], [http://pdbe.org/6nv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nv7 RCSB], [http://www.ebi.ac.uk/pdbsum/6nv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nv7 ProSAT]</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=6nv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nv7 OCA], [http://pdbe.org/6nv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nv7 RCSB], [http://www.ebi.ac.uk/pdbsum/6nv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nv7 ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]

OCA at 05:20, 10 October 2019

OCA — Thu, 10 Oct 2019 05:20:47 GMT

←Older revision		Revision as of 05:20, 10 October 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6nv7 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==BACE1 in complex with a macrocyclic inhibitor==
		+	<StructureSection load='6nv7' size='340' side='right'caption='[[6nv7]], [[Resolution\|resolution]] 2.13Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6nv7]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NV7 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=L3J:(E)-N-(2-methylpropylidene)-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}-D-threoninamide'>L3J</scene></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=6nv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nv7 OCA], [http://pdbe.org/6nv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nv7 RCSB], [http://www.ebi.ac.uk/pdbsum/6nv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nv7 ProSAT]</span></td></tr>
		+	</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACE1 (Beta-site Amyloid precursor protein (APP) Cleaving Enzyme 1) is a promising therapeutic target for Alzheimer's disease (AD). However, efficient expression, purification and crystallization systems are not well described or detailed in the literature nor are approaches for treatment of enzyme kinetic data for potent inhibitors well described. We therefore developed a platform for expression and purification of BACE1, including protein refolding from inclusion bodies, from E.coli in addition to optimizing a reproducible crystallization procedure of BACE1 bound with inhibitors. We also report a detailed approach to the proper analysis of enzyme kinetic data for compounds that exhibit either rapid-equilibrium or tight-binding mechanisms. Our methods allow for the purification of ~15 mg of BACE1 enzyme from 1 L of culture which is higher than reported yields in the current literature. To evaluate the data analysis approach developed here, a well-known potent inhibitor and two of its derivatives were tested, analyzed and compared. The inhibitory constants (Ki) obtained from the kinetic studies are in agreement with dissociation constants (Kd) that were also determined using isothermal titration calorimetry (ITC) experiments. The X-ray structures of these three compounds in complex with BACE1 were readily obtained and provide important insight into the structure and thermodynamics of the BACE1-inhibitor interactions.

-	~~Authors~~:	+	Development of an efficient enzyme production and structure-based discovery platform for BACE1 inhibitors.,Yen YC, Kammeyer A, Jensen KC, Tirlangi J, Ghosh AK, Mesecar AD Biochemistry. 2019 Sep 24. doi: 10.1021/acs.biochem.9b00714. PMID:31549827<ref>PMID:31549827</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6nv7" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Memapsin 2]]
		+	[[Category: Ghosh, A K]]
		+	[[Category: Mesecar, A D]]
		+	[[Category: Yen, Y C]]
		+	[[Category: Inhibitor complex]]
		+	[[Category: Peptide binding protein]]
		+	[[Category: Peptide binding protein-inhibitor complex]]
		+	[[Category: Protease]]

OCA at 05:09, 21 February 2019

OCA — Thu, 21 Feb 2019 05:09:10 GMT

←Older revision		Revision as of 05:09, 21 February 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6nv7 is ON HOLD	+	The entry 6nv7 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6nv7" [edit=sysop:move=sysop]

OCA — Wed, 13 Feb 2019 07:48:49 GMT

Protected "6nv7" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:48, 13 February 2019

OCA: New page: '''Unreleased structure''' The entry 6nv7 is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 13 Feb 2019 07:48:48 GMT

New page: '''Unreleased structure''' The entry 6nv7 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6nv7 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]