2fjp

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[[Image:2fjp.gif|left|200px]]
 
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{{Structure
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==Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor==
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|PDB= 2fjp |SIZE=350|CAPTION= <scene name='initialview01'>2fjp</scene>, resolution 2.40&Aring;
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<StructureSection load='2fjp' size='340' side='right'caption='[[2fjp]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S14:6-(4-{(1S,2S)-2-AMINO-1-[(DIMETHYLAMINO)CARBONYL]-3-[(3S)-3-FLUOROPYRROLIDIN-1-YL]-3-OXOPROPYL}PHENYL)-1H-[1,2,4]TRIAZOLO[1,5-A]PYRIDIN-4-IUM'>S14</scene>
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<table><tr><td colspan='2'>[[2fjp]] is a 2 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=2FJP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FJP FirstGlance]. <br>
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|ACTIVITY= <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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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|GENE= DPP4, ADCP2, CD26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=S14:6-(4-{(1S,2S)-2-AMINO-1-[(DIMETHYLAMINO)CARBONYL]-3-[(3S)-3-FLUOROPYRROLIDIN-1-YL]-3-OXOPROPYL}PHENYL)-1H-[1,2,4]TRIAZOLO[1,5-A]PYRIDIN-4-IUM'>S14</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2fjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjp OCA], [https://pdbe.org/2fjp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fjp RCSB], [https://www.ebi.ac.uk/pdbsum/2fjp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fjp ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fjp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjp OCA], [http://www.ebi.ac.uk/pdbsum/2fjp PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2fjp RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fj/2fjp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2fjp ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.
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'''Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor'''
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(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.,Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE J Med Chem. 2006 Jun 15;49(12):3614-27. PMID:16759103<ref>PMID:16759103</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2fjp" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.
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*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2FJP is a [[Single protein]] structure of 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=2FJP OCA].
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__TOC__
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</StructureSection>
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==Reference==
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(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1 ,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes., Edmondson SD, Mastracchio A, Mathvink RJ, He J, Harper B, Park YJ, Beconi M, Di Salvo J, Eiermann GJ, He H, Leiting B, Leone JF, Levorse DA, Lyons K, Patel RA, Patel SB, Petrov A, Scapin G, Shang J, Roy RS, Smith A, Wu JK, Xu S, Zhu B, Thornberry NA, Weber AE, J Med Chem. 2006 Jun 15;49(12):3614-27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16759103 16759103]
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[[Category: Dipeptidyl-peptidase IV]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Becker, J W.]]
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[[Category: Becker JW]]
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[[Category: Patel, S B.]]
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[[Category: Patel SB]]
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[[Category: Scapin, G.]]
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[[Category: Scapin G]]
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[[Category: alpha/beta]]
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[[Category: beta-propeller]]
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[[Category: dimer]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:03:43 2008''
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Current revision

Human dipeptidyl peptidase IV/CD26 in complex with an inhibitor

PDB ID 2fjp

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