5i7u - Revision history

OCA at 08:26, 23 August 2023

OCA — Wed, 23 Aug 2023 08:26:08 GMT

←Older revision		Revision as of 08:26, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i7u' size='340' side='right'caption='[[5i7u]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='5i7u' size='340' side='right'caption='[[5i7u]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i7u]] 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=5I7U OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I7U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i7u]] 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=5I7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I7U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6AJ:2-({2-[(3R)-3-AMINOPIPERIDIN-1-YL]-5-METHYL-6,9-DIOXO-5,6,7,9-TETRAHYDRO-1H-IMIDAZO[1,2-A]PURIN-1-YL}METHYL)-4-FLUOROBENZONITRILE'>6AJ</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]] 1.95Å</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='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6AJ:2-({2-[(3R)-3-AMINOPIPERIDIN-1-YL]-5-METHYL-6,9-DIOXO-5,6,7,9-TETRAHYDRO-1H-IMIDAZO[1,2-A]PURIN-1-YL}METHYL)-4-FLUOROBENZONITRILE'>6AJ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5i7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7u OCA], [https://pdbe.org/5i7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i7u RCSB], [https://www.ebi.ac.uk/pdbsum/5i7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7u 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=5i7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7u OCA], [~~http~~://pdbe.org/5i7u PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i7u RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i7u PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7u 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 27:		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 07:08, 3 June 2020

OCA — Wed, 03 Jun 2020 07:08:01 GMT

←Older revision		Revision as of 07:08, 3 June 2020
Line 1:		Line 1:

	==Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor==		==Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor==
-	<StructureSection load='5i7u' size='340' side='right' caption='[[5i7u]], [[Resolution\|resolution]] 1.95Å' scene=''>	+	<StructureSection load='5i7u' size='340' side='right'caption='[[5i7u]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i7u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7U OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I7U FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i7u]] 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=5I7U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I7U FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6AJ:2-({2-[(3R)-3-AMINOPIPERIDIN-1-YL]-5-METHYL-6,9-DIOXO-5,6,7,9-TETRAHYDRO-1H-IMIDAZO[1,2-A]PURIN-1-YL}METHYL)-4-FLUOROBENZONITRILE'>6AJ</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=6AJ:2-({2-[(3R)-3-AMINOPIPERIDIN-1-YL]-5-METHYL-6,9-DIOXO-5,6,7,9-TETRAHYDRO-1H-IMIDAZO[1,2-A]PURIN-1-YL}METHYL)-4-FLUOROBENZONITRILE'>6AJ</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='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=5i7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7u OCA], [http://pdbe.org/5i7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i7u RCSB], [http://www.ebi.ac.uk/pdbsum/5i7u 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=5i7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7u OCA], [http://pdbe.org/5i7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i7u RCSB], [http://www.ebi.ac.uk/pdbsum/5i7u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i7u ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 19:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 5i7u" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i7u" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Dipeptidyl peptidase 3D structures\|Dipeptidyl peptidase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 28:
	</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 15:26, 20 June 2016

OCA — Mon, 20 Jun 2016 15:26:13 GMT

←Older revision		Revision as of 15:26, 20 June 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i7u is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor==
		+	<StructureSection load='5i7u' size='340' side='right' caption='[[5i7u]], [[Resolution\|resolution]] 1.95Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i7u]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I7U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I7U FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6AJ:2-({2-[(3R)-3-AMINOPIPERIDIN-1-YL]-5-METHYL-6,9-DIOXO-5,6,7,9-TETRAHYDRO-1H-IMIDAZO[1,2-A]PURIN-1-YL}METHYL)-4-FLUOROBENZONITRILE'>6AJ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5i7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i7u OCA], [http://pdbe.org/5i7u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i7u RCSB], [http://www.ebi.ac.uk/pdbsum/5i7u 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 ==
		+	In our efforts to develop second generation DPP-4 inhibitors, we endeavored to identify distinct structures with long-acting (once weekly) potential. Taking advantage of X-ray cocrystal structures of sitagliptin and other DPP-4 inhibitors, such as alogliptin and linagliptin bound to DPP-4, and aided by molecular modeling, we designed several series of heterocyclic compounds as initial targets. During their synthesis, an unexpected chemical transformation provided a novel tricyclic scaffold that was beyond our original design. Capitalizing on this serendipitous discovery, we have elaborated this scaffold into a very potent and selective DPP-4 inhibitor lead series, as highlighted by compound 17c.

-	~~Authors: Scapin~~, G.	+	Discovery of Novel Tricyclic Heterocycles as Potent and Selective DPP-4 Inhibitors for the Treatment of Type 2 Diabetes.,Wu WL, Hao J, Domalski M, Burnett DA, Pissarnitski D, Zhao Z, Stamford A, Scapin G, Gao YD, Soriano A, Kelly TM, Yao Z, Powles MA, Chen S, Mei H, Hwa J ACS Med Chem Lett. 2016 Mar 12;7(5):498-501. doi: 10.1021/acsmedchemlett.6b00027., eCollection 2016 May 12. PMID:27190600<ref>PMID:27190600</ref>

-	~~Description: Human DPP4 in complex with~~ a ~~novel tricyclic hetero~~-~~cycle inhibitor~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5i7u" 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 at 01:57, 10 March 2016

OCA — Thu, 10 Mar 2016 01:57:51 GMT

←Older revision		Revision as of 01:57, 10 March 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i7u is ON HOLD	+	The entry 5i7u is ON HOLD until Paper Publication

	Authors: Scapin, G.		Authors: Scapin, G.

OCA: Protected "5i7u" [edit=sysop:move=sysop]

OCA — Fri, 26 Feb 2016 16:57:09 GMT

Protected "5i7u" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:57, 26 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i7u is ON HOLD Authors: Scapin, G. Description: Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor [[Category: Unreleased Structu...

OCA — Fri, 26 Feb 2016 16:57:08 GMT

New page: '''Unreleased structure''' The entry 5i7u is ON HOLD Authors: Scapin, G. Description: Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor [[Category: Unreleased Structu...

New page

'''Unreleased structure'''

The entry 5i7u is ON HOLD

Authors: Scapin, G.

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