1orw

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[[Image:1orw.png|left|200px]]
 
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{{STRUCTURE_1orw| PDB=1orw | SCENE= }}
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==Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor==
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<StructureSection load='1orw' size='340' side='right'caption='[[1orw]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1orw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ORW 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]] 2.84&#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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P2Y:(2S)-PYRROLIDIN-2-YLMETHYLAMINE'>P2Y</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1orw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1orw OCA], [https://pdbe.org/1orw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1orw RCSB], [https://www.ebi.ac.uk/pdbsum/1orw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1orw ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DPP4_PIG DPP4_PIG] 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 (By similarity). Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline.<ref>PMID:14719797</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/or/1orw_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=1orw 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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The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a unique multifunctional protein, acting as receptor, binding and proteolytic molecule. We have determined the sequence and 1.8 A crystal structure of native DP IV prepared from porcine kidney. The crystal structure reveals a 2-2-2 symmetric tetrameric assembly which depends on the natively glycosylated beta-propeller blade IV. The crystal structure indicates that tetramerization of DP IV is a key mechanism to regulate its interaction with other components. Each subunit comprises two structural domains, the N-terminal eight-bladed beta-propeller with open Velcro topology and the C-terminal alpha/beta-hydrolase domain. Analogy with the structurally related POP and tricorn protease suggests that substrates access the buried active site through the beta-propeller tunnel while products leave the active site through a separate side exit. A dipeptide mimicking inhibitor complexed to the active site discloses key determinants for substrate recognition, including a Glu-Glu motif that distinguishes DP IV as an aminopeptidase and an oxyanion trap that binds and activates the P(2)-carbonyl oxygen necessary for efficient postproline cleavage. We discuss active and nonactive site-directed inhibition strategies of this pharmaceutical target protein.
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===Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor===
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The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism.,Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth HU, Brandstetter H Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5063-8. Epub 2003 Apr 10. PMID:12690074<ref>PMID:12690074</ref>
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{{ABSTRACT_PUBMED_12690074}}
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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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==About this Structure==
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<div class="pdbe-citations 1orw" style="background-color:#fffaf0;"></div>
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[[1orw]] is a 4 chain structure of [[Dipeptidyl peptidase]] with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORW OCA].
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==See Also==
==See Also==
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*[[Dipeptidyl peptidase|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:012690074</ref><ref group="xtra">PMID:012892317</ref><references group="xtra"/>
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__TOC__
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[[Category: Dipeptidyl-peptidase IV]]
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</StructureSection>
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[[Category: Large Structures]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
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[[Category: Bode, W.]]
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[[Category: Bode W]]
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[[Category: Brandstetter, H.]]
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[[Category: Brandstetter H]]
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[[Category: Demuth, H U.]]
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[[Category: Demuth HU]]
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[[Category: Engel, M.]]
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[[Category: Engel M]]
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[[Category: Heiser, U.]]
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[[Category: Heiser U]]
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[[Category: Hoffmann, T.]]
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[[Category: Hoffmann T]]
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[[Category: Huber, R.]]
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[[Category: Huber R]]
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[[Category: Kiefersauer, R.]]
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[[Category: Kiefersauer R]]
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[[Category: Wagner, L.]]
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[[Category: Wagner L]]
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[[Category: Wermann, M.]]
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[[Category: Wermann M]]
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[[Category: Diabetes mellitus]]
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[[Category: Drug design]]
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[[Category: Hydrolase]]
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[[Category: Oxyanion hole]]
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[[Category: Serine protease]]
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[[Category: Substrate channeling]]
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Current revision

Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor

PDB ID 1orw

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