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[[Image:1orw.jpg|left|200px]]


{{Structure
==Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor==
|PDB= 1orw |SIZE=350|CAPTION= <scene name='initialview01'>1orw</scene>, resolution 2.84&Aring;
<StructureSection load='1orw' size='340' side='right'caption='[[1orw]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>
<table><tr><td colspan='2'>[[1orw]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ORW FirstGlance]. <br>
|ACTIVITY= [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]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.84&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P2Y:(2S)-PYRROLIDIN-2-YLMETHYLAMINE'>P2Y</scene>, <scene name='pdbligand=PHI:IODO-PHENYLALANINE'>PHI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1orw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1orw OCA], [https://pdbe.org/1orw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1orw RCSB], [https://www.ebi.ac.uk/pdbsum/1orw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1orw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DPP4_PIG DPP4_PIG] 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.<ref>PMID:14719797</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/or/1orw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1orw ConSurf].
<div style="clear:both"></div>


'''Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor'''
==See Also==
 
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
 
== References ==
==Overview==
<references/>
The membrane-bound glycoprotein dipeptidyl peptidase IV (DP IV, CD26) is a unique multifunctional protein, acting as receptor, binding and proteolytic molecule. We have determined the sequence and 1.8 A crystal structure of native DP IV prepared from porcine kidney. The crystal structure reveals a 2-2-2 symmetric tetrameric assembly which depends on the natively glycosylated beta-propeller blade IV. The crystal structure indicates that tetramerization of DP IV is a key mechanism to regulate its interaction with other components. Each subunit comprises two structural domains, the N-terminal eight-bladed beta-propeller with open Velcro topology and the C-terminal alpha/beta-hydrolase domain. Analogy with the structurally related POP and tricorn protease suggests that substrates access the buried active site through the beta-propeller tunnel while products leave the active site through a separate side exit. A dipeptide mimicking inhibitor complexed to the active site discloses key determinants for substrate recognition, including a Glu-Glu motif that distinguishes DP IV as an aminopeptidase and an oxyanion trap that binds and activates the P(2)-carbonyl oxygen necessary for efficient postproline cleavage. We discuss active and nonactive site-directed inhibition strategies of this pharmaceutical target protein.
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
1ORW is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ORW OCA].
 
==Reference==
The crystal structure of dipeptidyl peptidase IV (CD26) reveals its functional regulation and enzymatic mechanism., Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth HU, Brandstetter H, Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5063-8. Epub 2003 Apr 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12690074 12690074]
[[Category: Dipeptidyl-peptidase IV]]
[[Category: Single protein]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Bode, W.]]
[[Category: Bode W]]
[[Category: Brandstetter, H.]]
[[Category: Brandstetter H]]
[[Category: Demuth, H U.]]
[[Category: Demuth HU]]
[[Category: Engel, M.]]
[[Category: Engel M]]
[[Category: Heiser, U.]]
[[Category: Heiser U]]
[[Category: Hoffmann, T.]]
[[Category: Hoffmann T]]
[[Category: Huber, R.]]
[[Category: Huber R]]
[[Category: Kiefersauer, R.]]
[[Category: Kiefersauer R]]
[[Category: Wagner, L.]]
[[Category: Wagner L]]
[[Category: Wermann, M.]]
[[Category: Wermann M]]
[[Category: NAG]]
[[Category: PHI]]
[[Category: SO4]]
[[Category: diabetes mellitus]]
[[Category: drug design]]
[[Category: mechanism]]
[[Category: oxyanion hole]]
[[Category: serine protease]]
[[Category: substrate channeling]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:14:46 2008''

Latest revision as of 08:50, 17 April 2024

Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic InhibitorCrystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor

Structural highlights

1orw is a 4 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.84Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPP4_PIG 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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Bar J, Weber A, Hoffmann T, Stork J, Wermann M, Wagner L, Aust S, Gerhartz B, Demuth HU. Characterisation of human dipeptidyl peptidase IV expressed in Pichia pastoris. A structural and mechanistic comparison between the recombinant human and the purified porcine enzyme. Biol Chem. 2003 Dec;384(12):1553-63. PMID:14719797 doi:http://dx.doi.org/10.1515/BC.2003.172

1orw, resolution 2.84Å

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