3g0c
From Proteopedia
Crystal structure of dipeptidyl peptidase IV in complex with a pyrimidinedione inhibitor 1
Structural highlights
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.[1] [2] [3] [4] [5] [6] [7] [8] [9] 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 PubMedThe discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development. Design and Synthesis of Pyrimidinone and Pyrimidinedione Inhibitors of Dipeptidyl Peptidase IV.,Zhang Z, Wallace MB, Feng J, Stafford JA, Skene RJ, Shi L, Lee B, Aertgeerts K, Jennings A, Xu R, Kassel DB, Kaldor SW, Navre M, Webb DR, Gwaltney SL J Med Chem. 2010 Dec 27. PMID:21186796[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Dipeptidyl-peptidase IV | Homo sapiens | Aertgeerts, K | Feng, J | Gwaltney, S L | Jennings, A | Kaldor, S W | Kassel, D | Lee, B | Shi, L | Skene, R J | Stafford, J A | Wallace, M B | Webb, D R | Xu, R | Zhang, Z | Aminopeptidase | Cell membrane | Dpp4 | Glycoprotein | Hydrolase | Hydrolase-hydrolase inhibitor complex | Membrane | Protease | Pyrimidindione | Pyrimidinone | Secreted | Serine protease | Signal-anchor | Transmembrane
