5kby

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m (Protected "5kby" [edit=sysop:move=sysop])
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'''Unreleased structure'''
 
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The entry 5kby is ON HOLD
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==Crystal structure of dipeptidyl peptidase IV in complex with SYR-472==
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<StructureSection load='5kby' size='340' side='right' caption='[[5kby]], [[Resolution|resolution]] 2.24&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5kby]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KBY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KBY FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5AX:2-(ACETYLAMINO)-1,5-ANHYDRO-2-DEOXY-D-GLUCITOL'>5AX</scene>, <scene name='pdbligand=6RL:2-[[6-[(3~{R})-3-AZANYLPIPERIDIN-1-YL]-3-METHYL-2,4-BIS(OXIDANYLIDENE)PYRIMIDIN-1-YL]METHYL]-4-FLUORANYL-BENZENECARBONITRILE'>6RL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dipeptidyl-peptidase_IV Dipeptidyl-peptidase IV], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.14.5 3.4.14.5] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5kby FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kby OCA], [http://pdbe.org/5kby PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kby RCSB], [http://www.ebi.ac.uk/pdbsum/5kby PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kby ProSAT]</span></td></tr>
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</table>
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== Function ==
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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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4- and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and &gt;10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t1/2 for dissociation approximately 30 minutes). X-ray diffraction data indicated a non-covalent interaction between dipeptidyl peptidase and trelagliptin. Taken together, potent dipeptidyl peptidase inhibition may partially contribute to sustained efficacy of trelagliptin.
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Authors: Skene, R.J., Jennings, A.J.
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Trelagliptin (SYR-472, Zafatek), Novel Once-Weekly Treatment for Type 2 Diabetes, Inhibits Dipeptidyl Peptidase-4 (DPP-4) via a Non-Covalent Mechanism.,Grimshaw CE, Jennings A, Kamran R, Ueno H, Nishigaki N, Kosaka T, Tani A, Sano H, Kinugawa Y, Koumura E, Shi L, Takeuchi K PLoS One. 2016 Jun 21;11(6):e0157509. doi: 10.1371/journal.pone.0157509., eCollection 2016. PMID:27328054<ref>PMID:27328054</ref>
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Description: Crystal structure of dipeptidyl peptidase IV in complex with SYR-472
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Jennings, A.J]]
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<div class="pdbe-citations 5kby" style="background-color:#fffaf0;"></div>
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[[Category: Skene, R.J]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Dipeptidyl-peptidase IV]]
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[[Category: Jennings, A J]]
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[[Category: Skene, R J]]
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[[Category: Co-complex]]
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[[Category: Glp-1]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Metabolic disease]]
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[[Category: Peptidase]]

Revision as of 11:50, 14 July 2016

Crystal structure of dipeptidyl peptidase IV in complex with SYR-472

5kby, resolution 2.24Å

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