5i7u

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(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...)
Current revision (08:26, 23 August 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 5i7u is ON HOLD
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==Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor==
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<StructureSection load='5i7u' size='340' side='right'caption='[[5i7u]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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<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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
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<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>
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<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>
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</table>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Scapin, G.
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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>
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Description: Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Scapin, G]]
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<div class="pdbe-citations 5i7u" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Scapin G]]

Current revision

Human DPP4 in complex with a novel tricyclic hetero-cycle inhibitor

PDB ID 5i7u

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