3o95

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
m (Protected "3o95" [edit=sysop:move=sysop])
Current revision (06:02, 17 October 2024) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:3o95.jpg|left|200px]]
 
-
<!--
+
==Crystal Structure of Human DPP4 Bound to TAK-100==
-
The line below this paragraph, containing "STRUCTURE_3o95", creates the "Structure Box" on the page.
+
<StructureSection load='3o95' size='340' side='right'caption='[[3o95]], [[Resolution|resolution]] 2.85&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'>[[3o95]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O95 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]] 2.85&#8491;</td></tr>
-
-->
+
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=01T:[5-(AMINOMETHYL)-6-(2,2-DIMETHYLPROPYL)-2-ETHYL-4-(4-METHYLPHENYL)PYRIDIN-3-YL]ACETIC+ACID'>01T</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PRD_900017:triacetyl-beta-chitotriose'>PRD_900017</scene></td></tr>
-
{{STRUCTURE_3o95| PDB=3o95 | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3o95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o95 OCA], [https://pdbe.org/3o95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o95 RCSB], [https://www.ebi.ac.uk/pdbsum/3o95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o95 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://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>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Inhibition of dipeptidyl peptidase IV (DPP-4) is an exciting new approach for the treatment of diabetes. To date there has been no DPP-4 chemotype possessing a carboxy group that has progressed into clinical trials. Originating from the discovery of the structurally novel quinoline derivative 1, we designed novel pyridine derivatives containing a carboxy group. In our design, the carboxy group interacted with the targeted amino acid residues around the catalytic region and thereby increased the inhibitory activity. After further optimization, we identified a hydrate of [5-(aminomethyl)-6-(2,2-dimethylpropyl)-2-ethyl-4-(4-methylphenyl)pyridin- 3-yl]acetic acid (30c) as a potent and selective DPP-4 inhibitor. The desired interactions with the critical active-site residues, such as a salt-bridge interaction with Arg125, were confirmed by X-ray cocrystal structure analysis. In addition, compound 30c showed a desired preclinical safety profile, and it was encoded as TAK-100.
-
===Crystal Structure of Human DPP4 Bound to TAK-100===
+
Discovery of a 3-Pyridylacetic Acid Derivative (TAK-100) as a Potent, Selective and Orally Active Dipeptidyl Peptidase IV (DPP-4) Inhibitor.,Miyamoto Y, Banno Y, Yamashita T, Fujimoto T, Oi S, Moritoh Y, Asakawa T, Kataoka O, Yashiro H, Takeuchi K, Suzuki N, Ikedo K, Kosaka T, Tsubotani S, Tani A, Sasaki M, Funami M, Amano M, Yamamoto Y, Aertgeerts K, Yano J, Maezaki H J Med Chem. 2011 Jan 10. PMID:21218817<ref>PMID:21218817</ref>
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 3o95" style="background-color:#fffaf0;"></div>
-
<!--
+
==See Also==
-
The line below this paragraph, {{ABSTRACT_PUBMED_21218817}}, 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 21218817 is the PubMed ID number.
+
== References ==
-
-->
+
<references/>
-
{{ABSTRACT_PUBMED_21218817}}
+
__TOC__
-
 
+
</StructureSection>
-
==About this Structure==
+
-
[[3o95]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O95 OCA].
+
-
 
+
-
==Reference==
+
-
<ref group="xtra">PMID:21218817</ref><references group="xtra"/>
+
-
[[Category: Dipeptidyl-peptidase IV]]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Aertgeerts,K.]]
+
[[Category: Large Structures]]
-
[[Category: Yano, J K.]]
+
[[Category: Aertgeerts K]]
 +
[[Category: Yano JK]]

Current revision

Crystal Structure of Human DPP4 Bound to TAK-100

PDB ID 3o95

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3o95"
Personal tools