5i3w - Revision history

OCA at 08:22, 23 August 2023

2023-08-23T08:22:24Z

←Older revision		Revision as of 08:22, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i3w' size='340' side='right'caption='[[5i3w]], [[Resolution\|resolution]] 2.15Å' scene=''>		<StructureSection load='5i3w' size='340' side='right'caption='[[5i3w]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i3w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I3W OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I3W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i3w]] is a 1 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=5I3W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I3W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=68L:N-[(5S)-2-AMINO-3-(5,6-DIHYDRO-2H-PYRAN-3-YL)-5H-SPIRO[1-BENZOPYRANO[2,3-C]PYRIDINE-5,4-[1,3]OXAZOL]-7-YL]-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>68L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 2.15Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=68L:N-[(5S)-2-AMINO-3-(5,6-DIHYDRO-2H-PYRAN-3-YL)-5H-SPIRO[1-BENZOPYRANO[2,3-C]PYRIDINE-5,4-[1,3]OXAZOL]-7-YL]-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>68L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [https://pdbe.org/5i3w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [https://www.ebi.ac.uk/pdbsum/5i3w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3w ProSAT]</span></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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [~~http~~://pdbe.org/5i3w PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i3w PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3w 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 27:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Memapsin 2]]~~	+	[[Category: Long AM]]
-	[[Category: Long~~, A M~~]]	+	[[Category: Whittington DA]]
-	[[Category: Whittington~~, D A]]~~	+
-	~~[[Category: Alzheimer's disease]]~~	+
-	~~[[Category: Amyloid precursor protein]]~~	+
-	~~[[Category: Aspartic protease]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex~~]]	+

OCA at 08:44, 27 May 2020

2020-05-27T08:44:32Z

←Older revision		Revision as of 08:44, 27 May 2020
Line 1:		Line 1:

	==Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhibitor 2==		==Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhibitor 2==
-	<StructureSection load='5i3w' size='340' side='right' caption='[[5i3w]], [[Resolution\|resolution]] 2.15Å' scene=''>	+	<StructureSection load='5i3w' size='340' side='right'caption='[[5i3w]], [[Resolution\|resolution]] 2.15Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i3w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I3W OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I3W FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i3w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I3W OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I3W FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=68L:N-[(5S)-2-AMINO-3-(5,6-DIHYDRO-2H-PYRAN-3-YL)-5H-SPIRO[1-BENZOPYRANO[2,3-C]PYRIDINE-5,4-[1,3]OXAZOL]-7-YL]-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>68L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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" id="ligandDat"><scene name='pdbligand=68L:N-[(5S)-2-AMINO-3-(5,6-DIHYDRO-2H-PYRAN-3-YL)-5H-SPIRO[1-BENZOPYRANO[2,3-C]PYRIDINE-5,4-[1,3]OXAZOL]-7-YL]-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>68L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [http://pdbe.org/5i3w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [http://www.ebi.ac.uk/pdbsum/5i3w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3w ProSAT]</span></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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [http://pdbe.org/5i3w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [http://www.ebi.ac.uk/pdbsum/5i3w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5i3w" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i3w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Beta secretase 3D structures\|Beta secretase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Memapsin 2]]		[[Category: Memapsin 2]]
	[[Category: Long, A M]]		[[Category: Long, A M]]

OCA at 09:16, 1 November 2017

2017-11-01T09:16:32Z

←Older revision		Revision as of 09:16, 1 November 2017
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [http://pdbe.org/5i3w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [http://www.ebi.ac.uk/pdbsum/5i3w 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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [http://pdbe.org/5i3w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [http://www.ebi.ac.uk/pdbsum/5i3w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i3w ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 19:05, 10 May 2016

2016-05-10T19:05:02Z

←Older revision		Revision as of 19:05, 10 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i3w is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhibitor 2==
		+	<StructureSection load='5i3w' size='340' side='right' caption='[[5i3w]], [[Resolution\|resolution]] 2.15Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i3w]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I3W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I3W FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=68L:N-[(5S)-2-AMINO-3-(5,6-DIHYDRO-2H-PYRAN-3-YL)-5H-SPIRO[1-BENZOPYRANO[2,3-C]PYRIDINE-5,4-[1,3]OXAZOL]-7-YL]-5-CHLOROPYRIDINE-2-CARBOXAMIDE'>68L</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i3x\|5i3x]], [[5i3y\|5i3y]], [[5i3v\|5i3v]]</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=5i3w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i3w OCA], [http://pdbe.org/5i3w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i3w RCSB], [http://www.ebi.ac.uk/pdbsum/5i3w 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 ==
		+	Fragment-based drug discovery (FBDD) has become a widely used tool in small-molecule drug discovery efforts. One of the most commonly used biophysical methods in detecting weak binding of fragments is nuclear magnetic resonance (NMR) spectroscopy. In particular, FBDD performed with (19)F NMR-based methods has been shown to provide several advantages over (1)H NMR using traditional magnetization-transfer and/or two-dimensional methods. Here, we demonstrate the utility and power of (19)F-based fragment screening by detailing the identification of a second-site fragment through (19)F NMR screening that binds to a specific pocket of the aspartic acid protease, beta-secretase (BACE-1). The identification of this second-site fragment allowed the undertaking of a fragment-linking approach, which ultimately yielded a molecule exhibiting a more than 360-fold increase in potency while maintaining reasonable ligand efficiency and gaining much improved selectivity over cathepsin-D (CatD). X-ray crystallographic studies of the molecules demonstrated that the linked fragments exhibited binding modes consistent with those predicted from the targeted screening approach, through-space NMR data, and molecular modeling.

-	~~Authors:~~ Whittington, ~~D.A.~~, ~~Long~~, A.M.	+	Fragment-Linking Approach Using (19)F NMR Spectroscopy To Obtain Highly Potent and Selective Inhibitors of beta-Secretase.,Jordan JB, Whittington DA, Bartberger MD, Sickmier EA, Chen K, Cheng Y, Judd T J Med Chem. 2016 Apr 28;59(8):3732-49. doi: 10.1021/acs.jmedchem.5b01917. Epub, 2016 Apr 6. PMID:26978477<ref>PMID:26978477</ref>

-	~~Description: Crystal structure~~ of ~~BACE1 in complex with 2~~-~~aminooxazoline~~-~~3-azaxanthene inhibitor~~ 2	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Whittington, D.A]]	+	<div class="pdbe-citations 5i3w" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Long, A.M~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Memapsin 2]]
		+	[[Category: Long, A M]]
		+	[[Category: Whittington, D A]]
		+	[[Category: Alzheimer's disease]]
		+	[[Category: Amyloid precursor protein]]
		+	[[Category: Aspartic protease]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]

OCA at 13:20, 2 March 2016

2016-03-02T13:20:48Z

←Older revision		Revision as of 13:20, 2 March 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i3w is ON HOLD	+	The entry 5i3w is ON HOLD until Paper Publication

	Authors: Whittington, D.A., Long, A.M.		Authors: Whittington, D.A., Long, A.M.

OCA: Protected "5i3w" [edit=sysop:move=sysop]

2016-02-21T01:34:04Z

Protected "5i3w" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:34, 21 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i3w is ON HOLD Authors: Whittington, D.A., Long, A.M. Description: Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhib...

2016-02-21T01:34:02Z

New page: '''Unreleased structure''' The entry 5i3w is ON HOLD Authors: Whittington, D.A., Long, A.M. Description: Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhib...

New page

'''Unreleased structure'''

The entry 5i3w is ON HOLD

Authors: Whittington, D.A., Long, A.M.

Description: Crystal structure of BACE1 in complex with 2-aminooxazoline-3-azaxanthene inhibitor 2
[[Category: Unreleased Structures]]
[[Category: Whittington, D.A]]
[[Category: Long, A.M]]