View source for 3wqh


==Crystal Structure of human DPP-IV in complex with Anagliptin==
<StructureSection load='3wqh' size='340' side='right'caption='[[3wqh]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3wqh]] 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=3WQH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WQH FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</td></tr>
<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>, <scene name='pdbligand=SKK:N-[2-({2-[(2S)-2-CYANOPYRROLIDIN-1-YL]-2-OXOETHYL}AMINO)-2-METHYLPROPYL]-2-METHYLPYRAZOLO[1,5-A]PYRIMIDINE-6-CARBOXAMIDE'>SKK</scene></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=3wqh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wqh OCA], [https://pdbe.org/3wqh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wqh RCSB], [https://www.ebi.ac.uk/pdbsum/3wqh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wqh ProSAT]</span></td></tr>
</table>
== Function ==
[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;">
== Publication Abstract from PubMed ==
The single-crystal structure of anagliptin, N-[2-({2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl}amino)-2-methylpropyl]-2-methyl pyrazolo[1,5-a]pyrimidine-6-carboxamide, was determined. Two independent molecules were held together by intermolecular hydrogen bonds, and the absolute configuration of the 2-cyanopyrrolidine ring delivered from l-prolinamide was confirmed to be S. The interactions of anagliptin with DPP-4 were clarified by the co-crystal structure solved at 2.85 A resolution. Based on the structure determined by X-ray crystallography, the potency and selectivity of anagliptin were discussed, and an SAR study using anagliptin derivatives was performed.

Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions.,Watanabe YS, Yasuda Y, Kojima Y, Okada S, Motoyama T, Takahashi R, Oka M J Enzyme Inhib Med Chem. 2015 Jul 6:1-8. PMID:26147347<ref>PMID:26147347</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3wqh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Adachi H]]
[[Category: Motoyama T]]
[[Category: Oka M]]
[[Category: Okada S]]
[[Category: Takahashi R]]
[[Category: Watanabe YS]]