1r9n

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{{Seed}}
 
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[[Image:1r9n.png|left|200px]]
 
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==Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution==
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The line below this paragraph, containing "STRUCTURE_1r9n", creates the "Structure Box" on the page.
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<StructureSection load='1r9n' size='340' side='right'caption='[[1r9n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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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'>[[1r9n]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R9N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1R9N 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]] 2.3&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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{{STRUCTURE_1r9n| PDB=1r9n | 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=1r9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1r9n OCA], [https://pdbe.org/1r9n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1r9n RCSB], [https://www.ebi.ac.uk/pdbsum/1r9n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1r9n 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/r9/1r9n_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=1r9n 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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Dipeptidyl peptidase IV (DPPIV) is a member of the prolyl oligopeptidase family of serine proteases. DPPIV removes dipeptides from the N terminus of substrates, including many chemokines, neuropeptides, and peptide hormones. Specific inhibition of DPPIV is being investigated in human trials for the treatment of type II diabetes. To understand better the molecular determinants that underlie enzyme catalysis and substrate specificity, we report the crystal structures of DPPIV in the free form and in complex with the first 10 residues of the physiological substrate, Neuropeptide Y (residues 1-10; tNPY). The crystal structure of the free form of the enzyme reveals two potential channels through which substrates could access the active site-a so-called propeller opening, and side opening. The crystal structure of the DPPIV/tNPY complex suggests that bioactive peptides utilize the side opening unique to DPPIV to access the active site. Other structural features in the active site such as the presence of a Glu motif, a well-defined hydrophobic S1 subsite, and minimal long-range interactions explain the substrate recognition and binding properties of DPPIV. Moreover, in the DPPIV/tNPY complex structure, the peptide is not cleaved but trapped in a tetrahedral intermediate that occurs during catalysis. Conformational changes of S630 and H740 between DPPIV in its free form and in complex with tNPY were observed and contribute to the stabilization of the tetrahedral intermediate. Our results facilitate the design of potent, selective small molecule inhibitors of DPPIV that may yield compounds for the development of novel drugs to treat type II diabetes.
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===Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution===
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Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation.,Aertgeerts K, Ye S, Tennant MG, Kraus ML, Rogers J, Sang BC, Skene RJ, Webb DR, Prasad GS Protein Sci. 2004 Feb;13(2):412-21. Epub 2004 Jan 10. PMID:14718659<ref>PMID:14718659</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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<div class="pdbe-citations 1r9n" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_14718659}}, adds the Publication Abstract to the page
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*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 14718659 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_14718659}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1R9N is a [[Protein complex]] structure of sequences 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=1R9N OCA].
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==Reference==
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Crystal structure of human dipeptidyl peptidase IV in complex with a decapeptide reveals details on substrate specificity and tetrahedral intermediate formation., Aertgeerts K, Ye S, Tennant MG, Kraus ML, Rogers J, Sang BC, Skene RJ, Webb DR, Prasad GS, Protein Sci. 2004 Feb;13(2):412-21. Epub 2004 Jan 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/14718659 14718659]
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[[Category: Dipeptidyl-peptidase IV]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Aertgeerts, K.]]
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[[Category: Macaca mulatta]]
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[[Category: Collins, B.]]
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[[Category: Aertgeerts K]]
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[[Category: Prasad, G S.]]
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[[Category: Collins B]]
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[[Category: Rogers, J.]]
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[[Category: Prasad GS]]
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[[Category: Sang, B C.]]
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[[Category: Rogers J]]
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[[Category: Skene, R.]]
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[[Category: Sang B-C]]
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[[Category: Tennant, M G.]]
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[[Category: Skene R]]
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[[Category: Webb, D R.]]
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[[Category: Tennant MG]]
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[[Category: Ye, S.]]
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[[Category: Webb DR]]
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[[Category: Alpha/beta hydrolase]]
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[[Category: Ye S]]
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[[Category: Eight-bladed beta propeller]]
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[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 17:44:39 2008''
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Current revision

Crystal Structure of human dipeptidyl peptidase IV in complex with a decapeptide (tNPY) at 2.3 Ang. Resolution

PDB ID 1r9n

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