4pnz

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{{STRUCTURE_4pnz| PDB=4pnz | SCENE= }}
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==Human dipeptidyl peptidase IV/CD26 in complex with the long-acting inhibitor Omarigliptin (MK-3102)==
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===Human dipeptidyl peptidase IV/CD26 in complex with the long-acting inhibitor Omarigliptin (MK-3102)===
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<StructureSection load='4pnz' size='340' side='right' caption='[[4pnz]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24660890}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4pnz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PNZ OCA]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2VH:(2R,3S,5R)-5-[2-(METHYLSULFONYL)-2,6-DIHYDROPYRROLO[3,4-C]PYRAZOL-5(4H)-YL]-2-(2,4,5-TRIFLUOROPHENYL)TETRAHYDRO-2H-PYRAN-3-AMINE'>2VH</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADCP2, CD26, DPP4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pnz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pnz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pnz RCSB], [http://www.ebi.ac.uk/pdbsum/4pnz PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.
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==Function==
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Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes.,Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y, Krueger D, Bak A, Eiermann G, He J, Cox J, Hicks J, Lyons K, He H, Salituro G, Tong S, Patel S, Doss G, Petrov A, Wu J, Xu SS, Sewall C, Zhang X, Zhang B, Thornberry NA, Weber AE J Med Chem. 2014 Apr 2. PMID:24660890<ref>PMID:24660890</ref>
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[[http://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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==About this Structure==
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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[[4pnz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PNZ OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:024660890</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Dipeptidyl-peptidase IV]]
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[[Category: Human]]
[[Category: Scapin, G.]]
[[Category: Scapin, G.]]
[[Category: Yan, Y.]]
[[Category: Yan, Y.]]

Revision as of 06:58, 7 May 2014

Human dipeptidyl peptidase IV/CD26 in complex with the long-acting inhibitor Omarigliptin (MK-3102)

4pnz, resolution 1.90Å

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