4zsp - Revision history

OCA at 07:40, 18 May 2023

OCA — Thu, 18 May 2023 07:40:13 GMT

←Older revision		Revision as of 07:40, 18 May 2023
Line 3:		Line 3:
	<StructureSection load='4zsp' size='340' side='right'caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='4zsp' size='340' side='right'caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zsp]] is a 2 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=4ZSP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4ZSP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zsp]] 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=4ZSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZSP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RZ:N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE'>4RZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4RZ:N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE'>4RZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [https://pdbe.org/4zsp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [https://www.ebi.ac.uk/pdbsum/4zsp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsp ProSAT]</span></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='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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [~~http~~://pdbe.org/4zsp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4zsp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsp 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 ==
Line 28:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Memapsin 2]]~~	+	[[Category: Timm DE]]
-	[[Category: Timm~~, D E]]~~	+
-	~~[[Category: Aspartyl]]~~	+
-	~~[[Category: Beta-secretase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 08:51, 26 June 2019

OCA — Wed, 26 Jun 2019 08:51:54 GMT

←Older revision		Revision as of 08:51, 26 June 2019
Line 1:		Line 1:

	==BACE crystal structure with bicyclic aminothiazine inhibitor==		==BACE crystal structure with bicyclic aminothiazine inhibitor==
-	<StructureSection load='4zsp' size='340' side='right' caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>	+	<StructureSection load='4zsp' size='340' side='right'caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4zsp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4zsp]] is a 2 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=4ZSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RZ:N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE'>4RZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RZ:N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE'>4RZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [http://pdbe.org/4zsp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [http://www.ebi.ac.uk/pdbsum/4zsp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsp 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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [http://pdbe.org/4zsp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [http://www.ebi.ac.uk/pdbsum/4zsp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsp ProSAT]</span></td></tr>
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 4zsp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4zsp" 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: Large Structures]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]
	[[Category: Timm, D E]]		[[Category: Timm, D E]]

OCA at 17:07, 22 March 2017

OCA — Wed, 22 Mar 2017 17:07:42 GMT

←Older revision		Revision as of 17:07, 22 March 2017
Line 1:		Line 1:
		+
	==BACE crystal structure with bicyclic aminothiazine inhibitor==		==BACE crystal structure with bicyclic aminothiazine inhibitor==
	<StructureSection load='4zsp' size='340' side='right' caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>		<StructureSection load='4zsp' size='340' side='right' caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [http://www.ebi.ac.uk/pdbsum/4zsp PDBsum]</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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [http://pdbe.org/4zsp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [http://www.ebi.ac.uk/pdbsum/4zsp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zsp ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4zsp" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 14:01, 10 June 2015

OCA — Wed, 10 Jun 2015 14:01:37 GMT

←Older revision		Revision as of 14:01, 10 June 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==BACE crystal structure with bicyclic aminothiazine inhibitor==
		+	<StructureSection load='4zsp' size='340' side='right' caption='[[4zsp]], [[Resolution\|resolution]] 1.91Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4zsp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZSP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4RZ:N-[(4AS,6S,8AR)-2-AMINO-4A,5,6,7,8,8A-HEXAHYDRO-4H-3,1-BENZOTHIAZIN-6-YL]-3-CHLOROBENZAMIDE'>4RZ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4zsm\|4zsm]], [[4zsq\|4zsq]], [[4zsr\|4zsr]]</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=4zsp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zsp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4zsp RCSB], [http://www.ebi.ac.uk/pdbsum/4zsp PDBsum]</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 ==
		+	The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described.

-	~~The entry 4zsp is ON HOLD~~	+	Preparation and biological evaluation of conformationally constrained BACE1 inhibitors.,Winneroski LL, Schiffler MA, Erickson JA, May PC, Monk SA, Timm DE, Audia JE, Beck JP, Boggs LN, Borders AR, Boyer RD, Brier RA, Hudziak KJ, Klimkowski VJ, Garcia Losada P, Mathes BM, Stout SL, Watson BM, Mergott DJ Bioorg Med Chem. 2015 Jul 1;23(13):3260-8. doi: 10.1016/j.bmc.2015.04.062. Epub, 2015 May 6. PMID:26001341<ref>PMID:26001341</ref>

-	~~Authors: Timm~~, D.E.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: BACE crystal structure with bicyclic aminothiazine inhibitor~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: Timm, D.E]]	+	__TOC__
		+	</StructureSection>
		+	[[Category: Memapsin 2]]
		+	[[Category: Timm, D E]]
		+	[[Category: Aspartyl]]
		+	[[Category: Beta-secretase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Protease]]

OCA: Protected "4zsp" [edit=sysop:move=sysop]

OCA — Wed, 20 May 2015 11:07:32 GMT

Protected "4zsp" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:07, 20 May 2015

OCA: New page: '''Unreleased structure''' The entry 4zsp is ON HOLD Authors: Timm, D.E. Description: BACE crystal structure with bicyclic aminothiazine inhibitor Category: Unreleased Structures [...

OCA — Wed, 20 May 2015 11:07:31 GMT

New page: '''Unreleased structure''' The entry 4zsp is ON HOLD Authors: Timm, D.E. Description: BACE crystal structure with bicyclic aminothiazine inhibitor Category: Unreleased Structures [...

New page

'''Unreleased structure'''

The entry 4zsp is ON HOLD

Authors: Timm, D.E.

Description: BACE crystal structure with bicyclic aminothiazine inhibitor
[[Category: Unreleased Structures]]
[[Category: Timm, D.E]]