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5lls

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Revision as of 06:29, 16 October 2019

Porcine dipeptidyl peptidase IV in complex with 8-(3-aminopiperidin-1-yl)-7-[(2-bromophenyl)methyl]-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Structural highlights

5lls 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.
Ligands:	, ,
Activity:	Dipeptidyl-peptidase IV, with EC number 3.4.14.5
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]

Publication Abstract from PubMed

The binding kinetics and thermodynamics of dipeptidyl peptidase (DPP)-4 inhibitors (gliptins) were investigated using surface plasmon resonance and isothermal titration calorimetry. Binding of gliptins to DPP-4 is a rapid electrostatically driven process. Off-rates were generally slow partly because of reversible covalent bond formation by some gliptins, and partly because of strong and extensive interactions. Binding of all gliptins is enthalpy-dominated due to strong ionic interactions and strong solvent-shielded hydrogen bonds. Using a congeneric series of molecules which represented the intermediates in the lead optimization program of linagliptin, the onset of slow binding kinetics and development of the thermodynamic repertoire were analyzed in the context of incremental changes of the chemical structures. All compounds rapidly associated, and therefore the optimization of affinity and residence time is highly correlated. The major contributor to the increasing free energy of binding was a strong increase of binding enthalpy, whereas entropic contributions remained low and constant despite significant addition of lipophilicity.

Comparative Analysis of Binding Kinetics and Thermodynamics of Dipeptidyl Peptidase-4 Inhibitors and Their Relationship to Structure.,Schnapp G, Klein T, Hoevels Y, Bakker RA, Nar H J Med Chem. 2016 Aug 25;59(16):7466-77. doi: 10.1021/acs.jmedchem.6b00475. Epub, 2016 Aug 4. PMID:27438064^[2]

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

References

↑ 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
↑ Schnapp G, Klein T, Hoevels Y, Bakker RA, Nar H. Comparative Analysis of Binding Kinetics and Thermodynamics of Dipeptidyl Peptidase-4 Inhibitors and Their Relationship to Structure. J Med Chem. 2016 Aug 25;59(16):7466-77. doi: 10.1021/acs.jmedchem.6b00475. Epub, 2016 Aug 4. PMID:27438064 doi:http://dx.doi.org/10.1021/acs.jmedchem.6b00475

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5lls"

@@ Line 1: / Line 1: @@
 ==Porcine dipeptidyl peptidase IV in complex with 8-(3-aminopiperidin-1-yl)-7-[(2-bromophenyl)methyl]-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione==
-<StructureSection load='5lls' size='340' side='right' caption='[[5lls]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
+<StructureSection load='5lls' size='340' side='right'caption='[[5lls]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5lls]] is a 4 chain structure with 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=5LLS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LLS FirstGlance]. <br>
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 5lls" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
 == References ==
 <references/>
@@ Line 24: / Line 27: @@
 </StructureSection>
 [[Category: Dipeptidyl-peptidase IV]]
+[[Category: Large Structures]]
 [[Category: Sus scrofa]]
 [[Category: Blaesse, M]]

5lls

From Proteopedia

Revision as of 06:29, 16 October 2019

Porcine dipeptidyl peptidase IV in complex with 8-(3-aminopiperidin-1-yl)-7-[(2-bromophenyl)methyl]-1,3-dimethyl-2,3,6,7-tetrahydro-1H-purine-2,6-dione

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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