3e4a - Revision history

OCA at 12:58, 30 August 2023

2023-08-30T12:58:09Z

←Older revision		Revision as of 12:58, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='3e4a' size='340' side='right'caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3e4a' size='340' side='right'caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E4A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.6Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([https://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=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [https://pdbe.org/3e4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [https://www.ebi.ac.uk/pdbsum/3e4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4a ProSAT]</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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [https://pdbe.org/3e4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [https://www.ebi.ac.uk/pdbsum/3e4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4a ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN]] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>	+	[https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Insulysin~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Choi, S]]	+	[[Category: Synthetic construct]]
-	[[Category: Cuny~~, G D~~]]	+	[[Category: Choi S]]
-	[[Category: Leissring~~, M A~~]]	+	[[Category: Cuny GD]]
-	[[Category: Malito, E]]	+	[[Category: Leissring MA]]
-	[[Category: Tang~~, W J]]~~	+	[[Category: Malito E]]
-	~~[[Category: Hydrolase]]~~	+	[[Category: Tang WJ]]
-	~~[[Category: Hydroxamate]]~~	+
-	~~[[Category: Insulin]]~~	+
-	~~[[Category: Insulin degrading enzyme]]~~	+
-	~~[[Category: Metal-binding]]~~	+
-	~~[[Category: Metalloprotease]]~~	+
-	~~[[Category: Protease~~]]	+

OCA at 19:35, 20 October 2021

2021-10-20T19:35:17Z

←Older revision		Revision as of 19:35, 20 October 2021
Line 1:		Line 1:

	==Human IDE-inhibitor complex at 2.6 angstrom resolution==		==Human IDE-inhibitor complex at 2.6 angstrom resolution==
-	<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='3e4a' size='340' side='right'caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3e4a]] is a 4 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=3E4A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3E4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E4A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([https://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/Insulysin Insulysin], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [~~http~~://pdbe.org/3e4a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3e4a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4a ProSAT]</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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [https://pdbe.org/3e4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [https://www.ebi.ac.uk/pdbsum/3e4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4a ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN]] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>	+	[[https://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN]] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e4a_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e4a_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
Line 30:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 3e4a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3e4a" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Insulin-degrading enzyme 3D structures\|Insulin-degrading enzyme 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 36:		Line 39:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
		+	[[Category: Large Structures]]
	[[Category: Choi, S]]		[[Category: Choi, S]]
	[[Category: Cuny, G D]]		[[Category: Cuny, G D]]

OCA at 09:02, 25 October 2017

2017-10-25T09:02:14Z

←Older revision		Revision as of 09:02, 25 October 2017
Line 1:		Line 1:
		+
	==Human IDE-inhibitor complex at 2.6 angstrom resolution==		==Human IDE-inhibitor complex at 2.6 angstrom resolution==
	<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>
Line 6:		Line 7:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([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/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://pdbe.org/3e4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a 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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://pdbe.org/3e4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3e4a ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 29:		Line 30:
	</div>		</div>
	<div class="pdbe-citations 3e4a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 3e4a" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:26, 8 February 2016

2016-02-08T08:26:47Z

←Older revision		Revision as of 08:26, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E4A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3e4a]] is a 4 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=3E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E4A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([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/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a 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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://pdbe.org/3e4a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a PDBsum]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 18:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3e4a ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 28:		Line 28:
	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 3e4a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 35:		Line 36:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
	[[Category: Choi, S]]		[[Category: Choi, S]]

OCA at 21:57, 24 December 2014

2014-12-24T21:57:54Z

←Older revision		Revision as of 21:57, 24 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E4A FirstGlance]. <br>		<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E4A FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>
-	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a 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=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a PDBsum]</span></td></tr>
-	<table>	+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/IDE_HUMAN IDE_HUMAN]] Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.<ref>PMID:10684867</ref> <ref>PMID:17613531</ref> <ref>PMID:18986166</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 37:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
-	[[Category: Choi, S.]]	+	[[Category: Choi, S]]
-	[[Category: Cuny, G D.]]	+	[[Category: Cuny, G D]]
-	[[Category: Leissring, M A.]]	+	[[Category: Leissring, M A]]
-	[[Category: Malito, E.]]	+	[[Category: Malito, E]]
-	[[Category: Tang, W J.]]	+	[[Category: Tang, W J]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydroxamate]]		[[Category: Hydroxamate]]

OCA at 13:29, 29 September 2014

2014-09-29T13:29:30Z

←Older revision		Revision as of 13:29, 29 September 2014
Line 1:		Line 1:
-	[[~~Image:~~3e4a.~~png~~\|~~left~~\|200px]]	+	==Human IDE-inhibitor complex at 2.6 angstrom resolution==
		+	<StructureSection load='3e4a' size='340' side='right' caption='[[3e4a]], [[Resolution\|resolution]] 2.60Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3e4a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3E4A FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=DIO:1,4-DIETHYLENE+DIOXIDE'>DIO</scene>, <scene name='pdbligand=QIX:N~2~-[(2R)-4-(HYDROXYAMINO)-2-(2-NAPHTHYLMETHYL)-4-OXOBUTANOYL]-L-ARGINYLGLYCYLGLYCINAMIDE'>QIX</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IDE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Insulysin Insulysin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.56 3.4.24.56] </span></td></tr>
		+	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3e4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e4a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3e4a RCSB], [http://www.ebi.ac.uk/pdbsum/3e4a PDBsum]</span></td></tr>
		+	<table>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e4/3e4a_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	BACKGROUND: Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged. METHODOLOGY/PRINCIPAL FINDINGS: We used a rational design approach based on analysis of combinatorial peptide mixtures and focused compound libraries to develop novel peptide hydroxamic acid inhibitors of IDE. The resulting compounds are approximately 10(6) times more potent than existing inhibitors, non-toxic, and surprisingly selective for IDE vis-a-vis conventional zinc-metalloproteases. Crystallographic analysis of an IDE-inhibitor complex reveals a novel mode of inhibition based on stabilization of IDE's "closed," inactive conformation. We show further that pharmacological inhibition of IDE potentiates insulin signaling by a mechanism involving reduced catabolism of internalized insulin. CONCLUSIONS/SIGNIFICANCE: The inhibitors we describe are the first to potently and selectively inhibit IDE or indeed any member of this atypical zinc-metalloprotease superfamily. The distinctive structure of IDE's active site, and the mode of action of our inhibitors, suggests that it may be possible to develop inhibitors that cross-react minimally with conventional zinc-metalloproteases. Significantly, our results reveal that insulin signaling is normally regulated by IDE activity not only extracellularly but also within cells, supporting the longstanding view that IDE inhibitors could hold therapeutic value for the treatment of diabetes.

-	~~{{STRUCTURE_3e4a\| PDB=3e4a \| SCENE= }}~~	+	Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin.,Leissring MA, Malito E, Hedouin S, Reinstatler L, Sahara T, Abdul-Hay SO, Choudhry S, Maharvi GM, Fauq AH, Huzarska M, May PS, Choi S, Logan TP, Turk BE, Cantley LC, Manolopoulou M, Tang WJ, Stein RL, Cuny GD, Selkoe DJ PLoS One. 2010 May 7;5(5):e10504. PMID:20498699<ref>PMID:20498699</ref>

-	~~===Human IDE-inhibitor complex at 2.6 angstrom resolution===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_20498699}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3e4a]] is~~ a ~~4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Homo_sapiens Homo sapiens]~~. ~~Full crystallographic information is available from [http:~~/~~/oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].~~	+

	==See Also==		==See Also==
	*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]		*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:020498699<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Insulysin]]		[[Category: Insulysin]]

OCA at 09:32, 20 October 2012

2012-10-20T09:32:36Z

←Older revision		Revision as of 09:32, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[3e4a]] is a 4 chain structure ~~of [[Insulin-Degrading Enzyme]]~~ with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].	+	[[3e4a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].

	==See Also==		==See Also==

OCA: Protected "3e4a" [edit=sysop:move=sysop]

2012-07-25T23:12:23Z

Protected "3e4a" [edit=sysop:move=sysop]

←Older revision

Revision as of 23:12, 25 July 2012

OCA at 23:12, 25 July 2012

2012-07-25T23:12:22Z

←Older revision		Revision as of 23:12, 25 July 2012
Line 1:		Line 1:
-	{{Seed}}
	[[Image:3e4a.png\|left\|200px]]		[[Image:3e4a.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3e4a", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3e4a\| PDB=3e4a \| SCENE= }}		{{STRUCTURE_3e4a\| PDB=3e4a \| SCENE= }}

	===Human IDE-inhibitor complex at 2.6 angstrom resolution===		===Human IDE-inhibitor complex at 2.6 angstrom resolution===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_20498699}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 20498699 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_20498699}}		{{ABSTRACT_PUBMED_20498699}}

	==About this Structure==		==About this Structure==
-	~~3E4A~~ is a 4 ~~chains~~ structure with ~~sequences~~ from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].	+	[[3e4a]] is a 4 chain structure of [[Insulin-Degrading Enzyme]] with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].
		+
		+	==See Also==
		+	*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~20498699~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:020498699</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
Line 38:		Line 29:
	[[Category: Metalloprotease]]		[[Category: Metalloprotease]]
	[[Category: Protease]]		[[Category: Protease]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 18 11:05:03 2010''

OCA at 06:57, 18 August 2010

2010-08-18T06:57:29Z

←Older revision		Revision as of 06:57, 18 August 2010
Line 10:		Line 10:
	{{STRUCTURE_3e4a\| PDB=3e4a \| SCENE= }}		{{STRUCTURE_3e4a\| PDB=3e4a \| SCENE= }}

-	===Human IDE-inhibitor complex at 2.6 resolution===	+	===Human IDE-inhibitor complex at 2.6 angstrom resolution===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_20498699}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 20498699 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_20498699}}

	==About this Structure==		==About this Structure==
-	3E4A is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].	+	3E4A is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E4A OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:20498699</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
		+	[[Category: Choi, S.]]
		+	[[Category: Cuny, G D.]]
		+	[[Category: Leissring, M A.]]
	[[Category: Malito, E.]]		[[Category: Malito, E.]]
	[[Category: Tang, W J.]]		[[Category: Tang, W J.]]
-	[[Category: Cytoplasm]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydroxamate]]		[[Category: Hydroxamate]]
Line 27:		Line 38:
	[[Category: Metalloprotease]]		[[Category: Metalloprotease]]
	[[Category: Protease]]		[[Category: Protease]]
-	[[Category: X-ray crystallography]]
-	[[Category: Zinc]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Nov 4 20~~:14:~~44 2009~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Aug 18 11:05:03 2010''