5ism - Revision history

OCA at 14:08, 30 August 2023

OCA — Wed, 30 Aug 2023 14:08:06 GMT

←Older revision		Revision as of 14:08, 30 August 2023
Line 3:		Line 3:
	<StructureSection load='5ism' size='340' side='right'caption='[[5ism]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='5ism' size='340' side='right'caption='[[5ism]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ism]] 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=5ISM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5ISM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ism]] 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=5ISM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ISM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DG:(2R,3S,5R)-2-(2,5-DIFLUOROPHENYL)-5-(7H-PYRROLO[3,4 3,4]PYRAZOLO[1,5-A]PYRIMIDIN-8(9H)-YL)OXAN-3-AMINE'>6DG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i7u\|5i7u]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DG:(2R,3S,5R)-2-(2,5-DIFLUOROPHENYL)-5-(7H-PYRROLO[3,4 3,4]PYRAZOLO[1,5-A]PYRIMIDIN-8(9H)-YL)OXAN-3-AMINE'>6DG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5ism FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ism OCA], [https://pdbe.org/5ism PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ism RCSB], [https://www.ebi.ac.uk/pdbsum/5ism PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ism ProSAT]</span></td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=5ism FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ism OCA], [~~http~~://pdbe.org/5ism PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ism RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ism PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ism ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref>	+	[https://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 28:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Dipeptidyl-peptidase IV]]~~	+	[[Category: Homo sapiens]]
-	~~[[Category: Human~~]]	+
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Scapin, G]]	+	[[Category: Scapin G]]
-	~~[[Category: Diabetes]]~~	+
-	~~[[Category: Dpp4 inhibitor]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Structure-based drug design~~]]	+

OCA at 07:30, 3 June 2020

OCA — Wed, 03 Jun 2020 07:30:11 GMT

←Older revision		Revision as of 07:30, 3 June 2020
Line 1:		Line 1:

	==Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor==		==Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor==
-	<StructureSection load='5ism' size='340' side='right' caption='[[5ism]], [[Resolution\|resolution]] 2.00Å' scene=''>	+	<StructureSection load='5ism' size='340' side='right'caption='[[5ism]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ism]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ISM OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5ISM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ism]] 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=5ISM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5ISM FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DG:(2R,3S,5R)-2-(2,5-DIFLUOROPHENYL)-5-(7H-PYRROLO[3,4 3,4]PYRAZOLO[1,5-A]PYRIMIDIN-8(9H)-YL)OXAN-3-AMINE'>6DG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6DG:(2R,3S,5R)-2-(2,5-DIFLUOROPHENYL)-5-(7H-PYRROLO[3,4 3,4]PYRAZOLO[1,5-A]PYRIMIDIN-8(9H)-YL)OXAN-3-AMINE'>6DG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i7u\|5i7u]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i7u\|5i7u]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">DPP4, ADCP2, CD26 ([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/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=5ism FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ism OCA], [http://pdbe.org/5ism PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ism RCSB], [http://www.ebi.ac.uk/pdbsum/5ism PDBsum]</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=5ism FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ism OCA], [http://pdbe.org/5ism PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ism RCSB], [http://www.ebi.ac.uk/pdbsum/5ism PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ism ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 20:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 5ism" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ism" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dipeptidyl peptidase 3D structures\|Dipeptidyl peptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 25:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Dipeptidyl-peptidase IV]]		[[Category: Dipeptidyl-peptidase IV]]
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Scapin, G]]		[[Category: Scapin, G]]
	[[Category: Diabetes]]		[[Category: Diabetes]]

OCA at 17:00, 15 May 2016

OCA — Sun, 15 May 2016 17:00:23 GMT

←Older revision		Revision as of 17:00, 15 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ism is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor==
		+	<StructureSection load='5ism' size='340' side='right' caption='[[5ism]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ism]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ISM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ISM FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6DG:(2R,3S,5R)-2-(2,5-DIFLUOROPHENYL)-5-(7H-PYRROLO[3,4 3,4]PYRAZOLO[1,5-A]PYRIMIDIN-8(9H)-YL)OXAN-3-AMINE'>6DG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i7u\|5i7u]]</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </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=5ism FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ism OCA], [http://pdbe.org/5ism PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ism RCSB], [http://www.ebi.ac.uk/pdbsum/5ism PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/DPP4_HUMAN DPP4_HUMAN]] Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:10951221</ref> <ref>PMID:17549790</ref> <ref>PMID:10570924</ref> <ref>PMID:10900005</ref> <ref>PMID:11772392</ref> <ref>PMID:14691230</ref> <ref>PMID:16651416</ref> <ref>PMID:17287217</ref> <ref>PMID:18708048</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure-activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly dosing in humans.

-	~~Authors:~~ Scapin, G.	+	The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors.,Cox JM, Chu HD, Kuethe JT, Gao YD, Scapin G, Eiermann G, He H, Li X, Lyons KA, Metzger J, Petrov A, Wu JK, Xu S, Sinha-Roy R, Weber AE, Biftu T Bioorg Med Chem Lett. 2016 Jun 1;26(11):2622-6. doi: 10.1016/j.bmcl.2016.04.020. , Epub 2016 Apr 9. PMID:27106708<ref>PMID:27106708</ref>

-	~~Description: Human DPP4 in complex with a novel 5~~,~~5,6~~-~~tricyclic pyrrolidine inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5ism" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Dipeptidyl-peptidase IV]]
	[[Category: Scapin, G]]		[[Category: Scapin, G]]
		+	[[Category: Diabetes]]
		+	[[Category: Dpp4 inhibitor]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Structure-based drug design]]

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

OCA — Wed, 11 May 2016 00:52:05 GMT

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

←Older revision

Revision as of 00:52, 11 May 2016

OCA: New page: '''Unreleased structure''' The entry 5ism is ON HOLD until Paper Publication Authors: Scapin, G. Description: Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor [...

OCA — Wed, 11 May 2016 00:52:04 GMT

New page: '''Unreleased structure''' The entry 5ism is ON HOLD until Paper Publication Authors: Scapin, G. Description: Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor [...

New page

'''Unreleased structure'''

The entry 5ism is ON HOLD until Paper Publication

Authors: Scapin, G.

Description: Human DPP4 in complex with a novel 5,5,6-tricyclic pyrrolidine inhibitor
[[Category: Unreleased Structures]]
[[Category: Scapin, G]]