2oag

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[[Image:2oag.png|left|200px]]
 
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==Crystal structure of human dipeptidyl peptidase IV (DPPIV) with pyrrolidine-constrained phenethylamine 29g==
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The line below this paragraph, containing "STRUCTURE_2oag", creates the "Structure Box" on the page.
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<StructureSection load='2oag' size='340' side='right'caption='[[2oag]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2oag]] is a 4 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=2OAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OAG FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.3&#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=DLI:(3R,4S)-1-{6-[3-(METHYLSULFONYL)PHENYL]PYRIMIDIN-4-YL}-4-(2,4,5-TRIFLUOROPHENYL)PYRROLIDIN-3-AMINE'>DLI</scene></td></tr>
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{{STRUCTURE_2oag| PDB=2oag | SCENE= }}
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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=2oag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oag OCA], [https://pdbe.org/2oag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oag RCSB], [https://www.ebi.ac.uk/pdbsum/2oag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oag 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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oa/2oag_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2oag ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A novel series of pyrrolidine-constrained phenethylamines were developed as dipeptidyl peptidase IV (DPP4) inhibitors for the treatment of type 2 diabetes. The cyclohexene ring of lead-like screening hit 5 was replaced with a pyrrolidine to enable parallel chemistry, and protein co-crystal structural data guided the optimization of N-substituents. Employing this strategy, a &gt;400x improvement in potency over the initial hit was realized in rapid fashion. Optimized compounds are potent and selective inhibitors with excellent pharmacokinetic profiles. Compound 30 was efficacious in vivo, lowering blood glucose in ZDF rats that were allowed to feed freely on a mixed meal.
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===Crystal structure of human dipeptidyl peptidase IV (DPPIV) with pyrrolidine-constrained phenethylamine 29g===
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Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit.,Backes BJ, Longenecker K, Hamilton GL, Stewart K, Lai C, Kopecka H, von Geldern TW, Madar DJ, Pei Z, Lubben TH, Zinker BA, Tian Z, Ballaron SJ, Stashko MA, Mika AK, Beno DW, Kempf-Grote AJ, Black-Schaefer C, Sham HL, Trevillyan JM Bioorg Med Chem Lett. 2007 Apr 1;17(7):2005-12. Epub 2007 Jan 19. PMID:17276063<ref>PMID:17276063</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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The line below this paragraph, {{ABSTRACT_PUBMED_17276063}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2oag" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 17276063 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17276063}}
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==About this Structure==
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[[2oag]] is a 4 chain structure of [[Dipeptidyl peptidase]] 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=2OAG OCA].
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==See Also==
==See Also==
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*[[Dipeptidyl peptidase]]
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*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:17276063</ref><references group="xtra"/>
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__TOC__
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[[Category: Dipeptidyl-peptidase IV]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Backes, B J.]]
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[[Category: Large Structures]]
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[[Category: Hamilton, G L.]]
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[[Category: Backes BJ]]
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[[Category: Kopecka, H.]]
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[[Category: Hamilton GL]]
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[[Category: Lai, C.]]
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[[Category: Kopecka H]]
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[[Category: Longenecker, K L.]]
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[[Category: Lai C]]
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[[Category: Stewart, K D.]]
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[[Category: Longenecker KL]]
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[[Category: Hydrolase]]
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[[Category: Stewart KD]]
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[[Category: Inhibitor complex]]
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[[Category: Serine-peptidase]]
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Current revision

Crystal structure of human dipeptidyl peptidase IV (DPPIV) with pyrrolidine-constrained phenethylamine 29g

PDB ID 2oag

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