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| | <StructureSection load='2h04' size='340' side='right'caption='[[2h04]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2h04' size='340' side='right'caption='[[2h04]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2h04]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H04 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2h04]] is a 1 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=2H04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H04 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UN:{4-[2,2-BIS(5-METHYL-1,2,4-OXADIAZOL-3-YL)-3-PHENYLPROPYL]PHENYL}SULFAMIC+ACID'>4UN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2ho2|2ho2]], [[2ho3|2ho3]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4UN:{4-[2,2-BIS(5-METHYL-1,2,4-OXADIAZOL-3-YL)-3-PHENYLPROPYL]PHENYL}SULFAMIC+ACID'>4UN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPRB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></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=2h04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h04 OCA], [https://pdbe.org/2h04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h04 RCSB], [https://www.ebi.ac.uk/pdbsum/2h04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h04 ProSAT]</span></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=2h04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h04 OCA], [https://pdbe.org/2h04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h04 RCSB], [https://www.ebi.ac.uk/pdbsum/2h04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h04 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PTPRB_HUMAN PTPRB_HUMAN]] Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).<ref>PMID:19116766</ref> <ref>PMID:19136612</ref>
| + | [https://www.uniprot.org/uniprot/PTPRB_HUMAN PTPRB_HUMAN] Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).<ref>PMID:19116766</ref> <ref>PMID:19136612</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Amarasinghe KD]] |
| - | [[Category: Amarasinghe, K D]] | + | [[Category: Clark CM]] |
| - | [[Category: Clark, C M]] | + | [[Category: Evdokimov AG]] |
| - | [[Category: Evdokimov, A G]] | + | [[Category: Gray JL]] |
| - | [[Category: Gray, J L]] | + | [[Category: Maier MB]] |
| - | [[Category: Maier, M B]] | + | [[Category: Mekel M]] |
| - | [[Category: Mekel, M]] | + | [[Category: Nichols R]] |
| - | [[Category: Nichols, R]] | + | [[Category: Peters KG]] |
| - | [[Category: Peters, K G]] | + | [[Category: Pokross ME]] |
| - | [[Category: Pokross, M E]] | + | [[Category: Walter RL]] |
| - | [[Category: Walter, R L]] | + | |
| - | [[Category: Drug design]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Protein tyrosine phosphatase]]
| + | |
| - | [[Category: Sulfamic acid]]
| + | |
| - | [[Category: Wpd-loop]]
| + | |
| Structural highlights
Function
PTPRB_HUMAN Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin (By similarity).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The sulfamic acid phosphotyrosine mimetic was coupled with a previously known malonate template to obtain highly selective and potent inhibitors of HPTPbeta. Potentially hydrolyzable malonate ester functionalities were replaced with 1,2,4-oxadiazoles without a significant effect on HPTPbeta potency.
Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta.,Amarasinghe KK, Evdokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:16759857[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yacyshyn OK, Lai PF, Forse K, Teichert-Kuliszewska K, Jurasz P, Stewart DJ. Tyrosine phosphatase beta regulates angiopoietin-Tie2 signaling in human endothelial cells. Angiogenesis. 2009;12(1):25-33. doi: 10.1007/s10456-008-9126-0. Epub 2009 Jan 1. PMID:19116766 doi:10.1007/s10456-008-9126-0
- ↑ Mellberg S, Dimberg A, Bahram F, Hayashi M, Rennel E, Ameur A, Westholm JO, Larsson E, Lindahl P, Cross MJ, Claesson-Welsh L. Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis. FASEB J. 2009 May;23(5):1490-502. doi: 10.1096/fj.08-123810. Epub 2009 Jan 9. PMID:19136612 doi:http://dx.doi.org/10.1096/fj.08-123810
- ↑ Amarasinghe KK, Evdokimov AG, Xu K, Clark CM, Maier MB, Srivastava A, Colson AO, Gerwe GS, Stake GE, Howard BW, Pokross ME, Gray JL, Peters KG. Design and synthesis of potent, non-peptidic inhibitors of HPTPbeta. Bioorg Med Chem Lett. 2006 Aug 15;16(16):4252-6. Epub 2006 Jun 12. PMID:16759857 doi:10.1016/j.bmcl.2006.05.074
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