1orw

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (22:09, 26 March 2025) (edit) (undo)
 
(11 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:1orw.png|left|200px]]
 
-
<!--
+
==Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor==
-
The line below this paragraph, containing "STRUCTURE_1orw", creates the "Structure Box" on the page.
+
<StructureSection load='1orw' size='340' side='right'caption='[[1orw]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<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>
-
or leave the SCENE parameter empty for the default display.
+
</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>
-
-->
+
<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>
-
{{STRUCTURE_1orw| PDB=1orw | SCENE= }}
+
<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/initialview03.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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
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.
-
===Crystal Structure of Porcine Dipeptidyl Peptidase IV (CD26) in Complex with a Peptidomimetic Inhibitor===
+
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:12690074<ref>PMID:12690074</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1orw" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_12690074}}, adds the Publication Abstract to the page
+
*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
-
(as it appears on PubMed at http://www.pubmed.gov), where 12690074 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_12690074}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
[[Category: Large Structures]]
-
1ORW is a 4 chains structure of sequences 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==
+
-
<ref group="xtra">PMID:12690074</ref><references group="xtra"/>
+
-
[[Category: Dipeptidyl-peptidase IV]]
+
[[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: 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 Tue Feb 17 10:18:46 2009''
+

Current revision

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

PDB ID 1orw

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools