2qt9

Human dipeptidyl peptidase iv/cd26 in complex with a 4-aryl cyclohexylalanine inhibitor

spinqualitylabelsall models 2qt9, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2qt9 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 524, NA, NAG, NDG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function 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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline-specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice. 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV.,Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Duffy JL Bioorg Med Chem Lett. 2007 Nov 1;17(21):5806-11. Epub 2007 Aug 26. PMID:17851076 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dipeptidyl peptidase 3D structures

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