6uvp - Revision history

OCA at 07:59, 11 October 2023

OCA — Wed, 11 Oct 2023 07:59:17 GMT

←Older revision		Revision as of 07:59, 11 October 2023
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	<StructureSection load='6uvp' size='340' side='right'caption='[[6uvp]], [[Resolution\|resolution]] 1.56Å' scene=''>		<StructureSection load='6uvp' size='340' side='right'caption='[[6uvp]], [[Resolution\|resolution]] 1.56Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6uvp]] 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=6UVP OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6UVP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6uvp]] 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=6UVP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UVP FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QJJ:N-{(1S,2S)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJJ</scene>, <scene name='pdbligand=QJM:N-{(1R,2R)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.56Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QJJ:N-{(1S,2S)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJJ</scene>, <scene name='pdbligand=QJM:N-{(1R,2R)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6uvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvp OCA], [https://pdbe.org/6uvp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uvp RCSB], [https://www.ebi.ac.uk/pdbsum/6uvp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvp 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=6uvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvp OCA], [~~http~~://pdbe.org/6uvp PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6uvp RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6uvp PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvp 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 20:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 6uvp" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6uvp" 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: Hendle J]]
-	[[Category: Hendle, J]]	+	[[Category: Timm DE]]
-	[[Category: Timm~~, D E]]~~	+
-	~~[[Category: Complex]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-inhibitor complex]]~~	+
-	~~[[Category: Inhibitor]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 12:25, 1 January 2020

OCA — Wed, 01 Jan 2020 12:25:22 GMT

←Older revision		Revision as of 12:25, 1 January 2020
Line 3:		Line 3:
	<StructureSection load='6uvp' size='340' side='right'caption='[[6uvp]], [[Resolution\|resolution]] 1.56Å' scene=''>		<StructureSection load='6uvp' size='340' side='right'caption='[[6uvp]], [[Resolution\|resolution]] 1.56Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6uvp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UVP FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6uvp]] 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=6UVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UVP FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QJJ:N-{(1S,2S)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJJ</scene>, <scene name='pdbligand=QJM:N-{(1R,2R)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QJJ:N-{(1S,2S)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJJ</scene>, <scene name='pdbligand=QJM:N-{(1R,2R)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6uvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvp OCA], [http://pdbe.org/6uvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uvp RCSB], [http://www.ebi.ac.uk/pdbsum/6uvp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvp 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=6uvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvp OCA], [http://pdbe.org/6uvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uvp RCSB], [http://www.ebi.ac.uk/pdbsum/6uvp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvp ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]

OCA at 15:26, 11 December 2019

OCA — Wed, 11 Dec 2019 15:26:13 GMT

←Older revision		Revision as of 15:26, 11 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6uvp is ~~ON HOLD~~	+	==BACE-1 in complex with compound #3==
		+	<StructureSection load='6uvp' size='340' side='right'caption='[[6uvp]], [[Resolution\|resolution]] 1.56Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6uvp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6UVP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6UVP FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=QJJ:N-{(1S,2S)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJJ</scene>, <scene name='pdbligand=QJM:N-{(1R,2R)-2-[(4aS,7aR)-2-amino-4a,5-dihydro-4H-furo[3,4-d][1,3]thiazin-7a(7H)-yl]cyclopropyl}-5-fluoropyridine-2-carboxamide'>QJM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6uvp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uvp OCA], [http://pdbe.org/6uvp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6uvp RCSB], [http://www.ebi.ac.uk/pdbsum/6uvp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6uvp 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 ==
		+	Inhibition of BACE1 has become an important strategy in the quest for disease modifying agents to slow the progression of Alzheimer's disease. We previously reported the fragment-based discovery of LY2811376, the first BACE1 inhibitor reported to demonstrate robust reduction of human CSF Abeta in a Phase I clinical trial. We also reported on the discovery of LY2886721, a potent BACE1 inhibitor that reached phase 2 clinical trials. Herein we describe the preparation and structure activity relationships (SAR) of a series of BACE1 inhibitors utilizing trans-cyclopropyl moieties as conformational constraints. The design, details of the stereochemically complex organic synthesis, and biological activity of these BACE1 inhibitors is described.

-	~~Authors~~: ~~Hendle~~, J.	+	Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints.,Winneroski LL, Erickson JA, Green SJ, Lopez JE, Stout SL, Porter WJ, Timm DE, Audia JE, Barberis M, Beck JP, Boggs LN, Borders AR, Boyer RD, Brier RA, Hembre EJ, Hendle J, Garcia-Losada P, Minguez JM, Mathes BM, May PC, Monk SA, Rankovic Z, Shi Y, Watson BM, Yang Z, Mergott DJ Bioorg Med Chem. 2019 Nov 15:115194. doi: 10.1016/j.bmc.2019.115194. PMID:31786008<ref>PMID:31786008</ref>

-	~~Description: BACE~~-~~1 in complex with compound~~ #3	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6uvp" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Memapsin 2]]
	[[Category: Hendle, J]]		[[Category: Hendle, J]]
		+	[[Category: Timm, D E]]
		+	[[Category: Complex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-inhibitor complex]]
		+	[[Category: Inhibitor]]
		+	[[Category: Protease]]

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

OCA — Wed, 13 Nov 2019 09:36:31 GMT

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

←Older revision

Revision as of 09:36, 13 November 2019

OCA: New page: '''Unreleased structure''' The entry 6uvp is ON HOLD Authors: Hendle, J. Description: BACE-1 in complex with compound #3 Category: Unreleased Structures Category: Hendle, J

OCA — Wed, 13 Nov 2019 09:36:29 GMT

New page: '''Unreleased structure''' The entry 6uvp is ON HOLD Authors: Hendle, J. Description: BACE-1 in complex with compound #3 Category: Unreleased Structures Category: Hendle, J

New page

'''Unreleased structure'''

The entry 6uvp is ON HOLD

Authors: Hendle, J.

Description: BACE-1 in complex with compound #3
[[Category: Unreleased Structures]]
[[Category: Hendle, J]]