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2gbf

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Revision as of 00:38, 11 September 2015

rat dpp-IV with alkynyl cyanopyrrolidine #1

Structural highlights

2gbf is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2gbc, 2gbg, 2gbi
Activity:	Dipeptidyl-peptidase IV, with EC number 3.4.14.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[DPP4_RAT] 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 (By similarity). 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

Dipeptidyl peptidase IV (DPP-IV) belongs to a family of serine peptidases, and due to its indirect regulatory role in plasma glucose modulation, DPP-IV has become an attractive pharmaceutical target for diabetes therapy. DPP-IV inactivates the glucagon-like peptide (GLP-1) and several other naturally produced bioactive peptides that contain preferentially a proline or alanine residue in the second amino acid sequence position by cleaving the N-terminal dipeptide. To elucidate the details of the active site for structure-based drug design, we crystallized a natural source preparation of DPP-IV isolated from rat kidney and determined its three-dimensional structure using X-ray diffraction techniques. With a high degree of similarity to structures of human DPP-IV, the active site architecture provides important details for the design of inhibitory compounds, and structures of inhibitor-protein complexes offer detailed insight into three-dimensional structure-activity relationships that include a conformational change of Tyr548. Such accommodation is exemplified by the response to chemical substitution on 2-cyanopyrrolidine inhibitors at the 5 position, which conveys inhibitory selectivity for DPP-IV over closely related homologues. A similar conformational change is also observed in the complex with an unrelated synthetic inhibitor containing a xanthine core that is also selective for DPP-IV. These results suggest the conformational flexibility of Tyr548 is unique among protein family members and may be utilized in drug design to achieve peptidase selectivity.

Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors.,Longenecker KL, Stewart KD, Madar DJ, Jakob CG, Fry EH, Wilk S, Lin CW, Ballaron SJ, Stashko MA, Lubben TH, Yong H, Pireh D, Pei Z, Basha F, Wiedeman PE, von Geldern TW, Trevillyan JM, Stoll VS Biochemistry. 2006 Jun 20;45(24):7474-82. PMID:16768443^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Longenecker KL, Stewart KD, Madar DJ, Jakob CG, Fry EH, Wilk S, Lin CW, Ballaron SJ, Stashko MA, Lubben TH, Yong H, Pireh D, Pei Z, Basha F, Wiedeman PE, von Geldern TW, Trevillyan JM, Stoll VS. Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors. Biochemistry. 2006 Jun 20;45(24):7474-82. PMID:16768443 doi:http://dx.doi.org/10.1021/bi060184f

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gbf"

@@ Line 6: / Line 6: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gbc|2gbc]], [[2gbg|2gbg]], [[2gbi|2gbi]]</td></tr>
 <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>
-<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=2gbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gbf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2gbf RCSB], [http://www.ebi.ac.uk/pdbsum/2gbf PDBsum]</span></td></tr>
+<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=2gbf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gbf OCA], [http://pdbe.org/2gbf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gbf RCSB], [http://www.ebi.ac.uk/pdbsum/2gbf PDBsum]</span></td></tr>
 </table>
 == Function ==
@@ Line 28: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2gbf" style="background-color:#fffaf0;"></div>
 ==See Also==

2gbf

From Proteopedia

Revision as of 00:38, 11 September 2015

rat dpp-IV with alkynyl cyanopyrrolidine #1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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