4gsf - Revision history

OCA at 15:55, 14 March 2024

OCA — Thu, 14 Mar 2024 15:55:09 GMT

←Older revision		Revision as of 15:55, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gsf]] 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GSF FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gsf]] 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GSF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</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]] 2.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [https://pdbe.org/4gsf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [https://www.ebi.ac.uk/pdbsum/4gsf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsf 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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [https://pdbe.org/4gsf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [https://www.ebi.ac.uk/pdbsum/4gsf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsf 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>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-a and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-a clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.
-
-	Structure-activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme.,Charton J, Gauriot M, Totobenazara J, Hennuyer N, Dumont J, Bosc D, Marechal X, Elbakali J, Herledan A, Wen X, Ronco C, Gras-Masse H, Heninot A, Pottiez V, Landry V, Staels B, Liang WG, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R Eur J Med Chem. 2015 Jan 27;90:547-67. doi: 10.1016/j.ejmech.2014.12.005. Epub, 2014 Dec 4. PMID:25489670<ref>PMID:25489670</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4gsf" style="background-color:#fffaf0;"></div>

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

OCA at 07:14, 26 October 2022

OCA — Wed, 26 Oct 2022 07:14:55 GMT

←Older revision		Revision as of 07:14, 26 October 2022
Line 1:		Line 1:

	==The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester==		==The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester==
-	<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>	+	<StructureSection load='4gsf' size='340' side='right'caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gsf]] 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GSF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gsf]] 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GSF FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</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=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gs8\|4gs8]], [[4gsc\|4gsc]], [[4gse\|4gse]]</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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [https://pdbe.org/4gsf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [https://www.ebi.ac.uk/pdbsum/4gsf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsf ProSAT]</span></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='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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [~~http~~://pdbe.org/4gsf PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gsf PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsf 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 20:

	==See Also==		==See Also==
-	*[[Insulin-~~Degrading Enzyme~~\|Insulin-~~Degrading Enzyme~~]]	+	*[[Insulin-degrading enzyme 3D structures\|Insulin-degrading enzyme 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Insulysin~~]]	+	[[Category: Large Structures]]
-	[[Category: Deprez, B]]	+	[[Category: Deprez B]]
-	[[Category: Deprez-Poulain, R]]	+	[[Category: Deprez-Poulain R]]
-	[[Category: Guo, Q]]	+	[[Category: Guo Q]]
-	[[Category: Tang~~, W J]]~~	+	[[Category: Tang WJ]]
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Insulin degrading enzyme~~]]	+

OCA at 17:07, 22 March 2017

OCA — Wed, 22 Mar 2017 17:07:41 GMT

←Older revision		Revision as of 17:07, 22 March 2017
Line 1:		Line 1:
		+
	==The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester==		==The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester==
	<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>
Line 7:		Line 8:
	<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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf 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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://pdbe.org/4gsf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gsf ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	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 4gsf" style="background-color:#fffaf0;"></div>

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

OCA at 08:58, 17 June 2015

OCA — Wed, 17 Jun 2015 08:58:17 GMT

←Older revision		Revision as of 08:58, 17 June 2015
Line 2:		Line 2:
	<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gsf]] is a 2 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GSF FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gsf]] 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GSF FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</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=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gs8\|4gs8]], [[4gsc\|4gsc]], [[4gse\|4gse]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gs8\|4gs8]], [[4gsc\|4gsc]], [[4gse\|4gse]]</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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf 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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf PDBsum]</span></td></tr>
Line 11:		Line 11:
	== 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>		[[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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Insulin degrading enzyme (IDE) is a zinc metalloprotease that degrades small amyloid peptides such as amyloid-a and insulin. So far the dearth of IDE-specific pharmacological inhibitors impacts the understanding of its role in the physiopathology of Alzheimer's disease, amyloid-a clearance, and its validation as a potential therapeutic target. Hit 1 was previously discovered by high-throughput screening. Here we describe the structure-activity study, that required the synthesis of 48 analogues. We found that while the carboxylic acid, the imidazole and the tertiary amine were critical for activity, the methyl ester was successfully optimized to an amide or a 1,2,4-oxadiazole. Along with improving their activity, compounds were optimized for solubility, lipophilicity and stability in plasma and microsomes. The docking or co-crystallization of some compounds at the exosite or the catalytic site of IDE provided the structural basis for IDE inhibition. The pharmacokinetic properties of best compounds 44 and 46 were measured in vivo. As a result, 44 (BDM43079) and its methyl ester precursor 48 (BDM43124) are useful chemical probes for the exploration of IDE's role.
		+
		+	Structure-activity relationships of imidazole-derived 2-[N-carbamoylmethyl-alkylamino]acetic acids, dual binders of human insulin-degrading enzyme.,Charton J, Gauriot M, Totobenazara J, Hennuyer N, Dumont J, Bosc D, Marechal X, Elbakali J, Herledan A, Wen X, Ronco C, Gras-Masse H, Heninot A, Pottiez V, Landry V, Staels B, Liang WG, Leroux F, Tang WJ, Deprez B, Deprez-Poulain R Eur J Med Chem. 2015 Jan 27;90:547-67. doi: 10.1016/j.ejmech.2014.12.005. Epub, 2014 Dec 4. PMID:25489670<ref>PMID:25489670</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
Line 18:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
	[[Category: Deprez, B]]		[[Category: Deprez, B]]

OCA at 23:51, 24 December 2014

OCA — Wed, 24 Dec 2014 23:51:29 GMT

←Older revision		Revision as of 23:51, 24 December 2014
Line 9:		Line 9:
	<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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf 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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf 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>

	==See Also==		==See Also==
	*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]		*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 11:48, 21 December 2014

OCA — Sun, 21 Dec 2014 11:48:14 GMT

←Older revision		Revision as of 11:48, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4gsf\| PDB=4gsf \| SCENE= }}~~	+	==The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester==
-	===The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester===	+	<StructureSection load='4gsf' size='340' side='right' caption='[[4gsf]], [[Resolution\|resolution]] 2.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4gsf]] is a 2 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=4GSF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GSF FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MGH:METHYL+N-(CARBOXYMETHYL)-N-(3-PHENYLPROPANOYL)GLYCYL-D-HISTIDINATE'>MGH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4gs8\|4gs8]], [[4gsc\|4gsc]], [[4gse\|4gse]]</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='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=4gsf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gsf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gsf RCSB], [http://www.ebi.ac.uk/pdbsum/4gsf PDBsum]</span></td></tr>
		+	</table>

-	==~~Function~~==	+	==See Also==
-	[[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>~~	+	*[[Insulin-Degrading Enzyme\|Insulin-Degrading Enzyme]]
-		+	__TOC__
-	~~==About this Structure==~~	+	</StructureSection>
-	~~[[4gsf~~]] is a 2 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=4GSF OCA].	+
-		+
-	~~==Reference==~~	+
-	~~<references group="xtra"/>~~<~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Insulysin]]		[[Category: Insulysin]]
-	[[Category: Deprez, B.]]	+	[[Category: Deprez, B]]
-	[[Category: Deprez-Poulain, R.]]	+	[[Category: Deprez-Poulain, R]]
-	[[Category: Guo, Q.]]	+	[[Category: Guo, Q]]
-	[[Category: Tang, W J.]]	+	[[Category: Tang, W J]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Insulin degrading enzyme]]		[[Category: Insulin degrading enzyme]]

OCA at 07:37, 28 August 2013

OCA — Wed, 28 Aug 2013 07:37:16 GMT

←Older revision		Revision as of 07:37, 28 August 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4gsf\| PDB=4gsf \| SCENE= }}
		+	===The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester===

-	~~The entry 4gsf is ON HOLD~~ ~~until Paper Publication~~	+	==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>

-	~~Authors~~: ~~Guo, Q~~.~~, Deprez-Poulain, R~~.~~, Deprez, B~~.~~, Tang, W~~.J.	+	==About this Structure==
		+	[[4gsf]] is a 2 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=4GSF OCA].

-	~~Description~~: ~~The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-~~[~~carboxymethyl~~-~~(3-phenyl-propionyl)-amino~~]-~~acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Insulysin]]
		+	[[Category: Deprez, B.]]
		+	[[Category: Deprez-Poulain, R.]]
		+	[[Category: Guo, Q.]]
		+	[[Category: Tang, W J.]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Insulin degrading enzyme]]

OCA at 06:12, 14 November 2012

OCA — Wed, 14 Nov 2012 06:12:57 GMT

←Older revision		Revision as of 06:12, 14 November 2012
Line 3:		Line 3:
	The entry 4gsf is ON HOLD until Paper Publication		The entry 4gsf is ON HOLD until Paper Publication

-	Authors: Guo, Q., Tang, W.J.	+	Authors: Guo, Q., Deprez-Poulain, R., Deprez, B., Tang, W.J.

	Description: The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester		Description: The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester

OCA at 06:53, 10 October 2012

OCA — Wed, 10 Oct 2012 06:53:27 GMT

←Older revision		Revision as of 06:53, 10 October 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4gsf is ON HOLD	+	The entry 4gsf is ON HOLD until Paper Publication

	Authors: Guo, Q., Tang, W.J.		Authors: Guo, Q., Tang, W.J.

	Description: The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester		Description: The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester

OCA at 05:44, 3 October 2012

OCA — Wed, 03 Oct 2012 05:44:55 GMT

←Older revision		Revision as of 05:44, 3 October 2012
Line 5:		Line 5:
	Authors: Guo, Q., Tang, W.J.		Authors: Guo, Q., Tang, W.J.

-	Description: ~~THE STRUCTURE ANALYSIS OF CYSTEINE FREE INSULIN DEGRADING ENZYME~~ (~~IDE~~) ~~WITH~~ (S)-2-{2-[~~CARBOXYMETHYL~~-(3-~~PHENYL~~-~~PROPIONYL~~)-~~AMINO~~]-~~ACETYLAMINO~~}-3-(3H-~~IMIDAZOL~~-4-YL)-~~PROPIONIC ACID METHYL ESTER~~	+	Description: The structure analysis of cysteine free insulin degrading enzyme (ide) with (s)-2-{2-[carboxymethyl-(3-phenyl-propionyl)-amino]-acetylamino}-3-(3h-imidazol-4-yl)-propionic acid methyl ester