6dhc - Revision history

OCA at 11:01, 1 January 2020

OCA — Wed, 01 Jan 2020 11:01:48 GMT

←Older revision		Revision as of 11:01, 1 January 2020
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	==X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand==		==X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand==
-	<StructureSection load='6dhc' size='340' side='right' caption='[[6dhc]], [[Resolution\|resolution]] 2.85Å' scene=''>	+	<StructureSection load='6dhc' size='340' side='right'caption='[[6dhc]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6dhc]] 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=6DHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DHC FirstGlance]. <br>		<table><tr><td colspan='2'>[[6dhc]] 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=6DHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DHC FirstGlance]. <br>
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	</div>		</div>
	<div class="pdbe-citations 6dhc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6dhc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta secretase 3D structures\|Beta secretase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]
	[[Category: Lendy, E K]]		[[Category: Lendy, E K]]

OCA at 06:35, 22 August 2018

OCA — Wed, 22 Aug 2018 06:35:11 GMT

←Older revision		Revision as of 06:35, 22 August 2018
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	<StructureSection load='6dhc' size='340' side='right' caption='[[6dhc]], [[Resolution\|resolution]] 2.85Å' scene=''>		<StructureSection load='6dhc' size='340' side='right' caption='[[6dhc]], [[Resolution\|resolution]] 2.85Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6dhc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DHC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6dhc]] 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=6DHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DHC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GHJ:(3R,3aR,6aS)-N-[(4R,7S,8S,10R,13S)-8-hydroxy-10,17-dimethyl-7-(2-methylpropyl)-5,11,14-trioxo-13-(propan-2-yl)-2-thia-6,12,15-triazaoctadecan-4-yl]hexahydrofuro[3,2-d][1,2]oxazole-3-carboxamide'>GHJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GHJ:(3R,3aR,6aS)-N-[(4R,7S,8S,10R,13S)-8-hydroxy-10,17-dimethyl-7-(2-methylpropyl)-5,11,14-trioxo-13-(propan-2-yl)-2-thia-6,12,15-triazaoctadecan-4-yl]hexahydrofuro[3,2-d][1,2]oxazole-3-carboxamide'>GHJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</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=6dhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dhc OCA], [http://pdbe.org/6dhc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dhc RCSB], [http://www.ebi.ac.uk/pdbsum/6dhc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dhc 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=6dhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dhc OCA], [http://pdbe.org/6dhc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dhc RCSB], [http://www.ebi.ac.uk/pdbsum/6dhc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dhc ProSAT]</span></td></tr>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]
	[[Category: Lendy, E K]]		[[Category: Lendy, E K]]

OCA at 07:19, 25 July 2018

OCA — Wed, 25 Jul 2018 07:19:34 GMT

←Older revision		Revision as of 07:19, 25 July 2018
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-	'''Unreleased structure'''

-	~~The entry~~ 6dhc is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand==
		+	<StructureSection load='6dhc' size='340' side='right' caption='[[6dhc]], [[Resolution\|resolution]] 2.85Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6dhc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DHC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DHC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GHJ:(3R,3aR,6aS)-N-[(4R,7S,8S,10R,13S)-8-hydroxy-10,17-dimethyl-7-(2-methylpropyl)-5,11,14-trioxo-13-(propan-2-yl)-2-thia-6,12,15-triazaoctadecan-4-yl]hexahydrofuro[3,2-d][1,2]oxazole-3-carboxamide'>GHJ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=URE:UREA'>URE</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=6dhc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dhc OCA], [http://pdbe.org/6dhc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6dhc RCSB], [http://www.ebi.ac.uk/pdbsum/6dhc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6dhc 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 ==
		+	We describe the design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors containing bicyclic isoxazoline carboxamides as the P3 ligand in combination with methyl cysteine, methylsulfonylalanine and Boc-amino alanine as P2 ligands. Inhibitor 3a displayed a BACE1 Ki value of 10.9nM and EC50 of 343nM. The X-ray structure of 3a bound to the active site of BACE1 was determined at 2.85A resolution. The structure revealed that the major molecular interactions between BACE1 and the bicyclic tetrahydrofuranyl isoxazoline heterocycle are van der Waals in nature.

-	~~Authors: Mesecar~~, ~~A.D~~., Lendy, E.K.	+	Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand.,Ghosh AK, Ghosh K, Brindisi M, Lendy EK, Yen YC, Kumaragurubaran N, Huang X, Tang J, Mesecar AD Bioorg Med Chem Lett. 2018 Jun 26. pii: S0960-894X(18)30546-8. doi:, 10.1016/j.bmcl.2018.06.045. PMID:29970308<ref>PMID:29970308</ref>

-	~~Description: X-ray structure~~ of ~~BACE1 in complex with a bicyclic isoxazoline carboxamide as~~ the ~~P3 ligand~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Mesecar, A.D]]	+	<div class="pdbe-citations 6dhc" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Lendy, E.K~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Memapsin 2]]
		+	[[Category: Lendy, E K]]
		+	[[Category: Mesecar, A D]]
		+	[[Category: Bace1]]
		+	[[Category: Hydrolase]]
		+	[[Category: Memepsin 2]]

OCA at 05:19, 18 July 2018

OCA — Wed, 18 Jul 2018 05:19:41 GMT

←Older revision		Revision as of 05:19, 18 July 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Mesecar, A.D., Lendy, E.K.		Authors: Mesecar, A.D., Lendy, E.K.

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

OCA — Wed, 30 May 2018 04:07:27 GMT

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

←Older revision

Revision as of 04:07, 30 May 2018

OCA: New page: '''Unreleased structure''' The entry 6dhc is ON HOLD Authors: Mesecar, A.D., Lendy, E.K. Description: X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the...

OCA — Wed, 30 May 2018 04:07:25 GMT

New page: '''Unreleased structure''' The entry 6dhc is ON HOLD Authors: Mesecar, A.D., Lendy, E.K. Description: X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the...

New page

'''Unreleased structure'''

The entry 6dhc is ON HOLD

Authors: Mesecar, A.D., Lendy, E.K.

Description: X-ray structure of BACE1 in complex with a bicyclic isoxazoline carboxamide as the P3 ligand
[[Category: Unreleased Structures]]
[[Category: Mesecar, A.D]]
[[Category: Lendy, E.K]]