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| | <StructureSection load='2vx1' size='340' side='right'caption='[[2vx1]], [[Resolution|resolution]] 1.65Å' scene=''> | | <StructureSection load='2vx1' size='340' side='right'caption='[[2vx1]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vx1]] 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=2VX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VX1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vx1]] 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=2VX1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VX1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7X8:3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE'>7X8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.65Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2bba|2bba]], [[2vwu|2vwu]], [[2vwv|2vwv]], [[2vwy|2vwy]], [[2vww|2vww]], [[2vwx|2vwx]], [[2vwz|2vwz]], [[2vx0|2vx0]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7X8:3-({4-[(5-CHLORO-1,3-BENZODIOXOL-4-YL)AMINO]PYRIMIDIN-2-YL}AMINO)BENZAMIDE'>7X8</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </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=2vx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vx1 OCA], [https://pdbe.org/2vx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vx1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vx1 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=2vx1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vx1 OCA], [https://pdbe.org/2vx1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vx1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vx1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vx1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/EPHB4_HUMAN EPHB4_HUMAN]] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis.<ref>PMID:12734395</ref> <ref>PMID:16424904</ref>
| + | [https://www.uniprot.org/uniprot/EPHB4_HUMAN EPHB4_HUMAN] Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis.<ref>PMID:12734395</ref> <ref>PMID:16424904</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: Receptor protein-tyrosine kinase]]
| + | [[Category: Barratt D]] |
| - | [[Category: Barratt, D]] | + | [[Category: Brassington CA]] |
| - | [[Category: Brassington, C A]] | + | [[Category: Green I]] |
| - | [[Category: Green, I]] | + | [[Category: Kettle JG]] |
| - | [[Category: Kettle, J G]] | + | [[Category: Leach AG]] |
| - | [[Category: Leach, A G]] | + | [[Category: McCall EJ]] |
| - | [[Category: McCall, E J]] | + | [[Category: Read J]] |
| - | [[Category: Read, J]] | + | [[Category: Valentine AL]] |
| - | [[Category: Valentine, A L]] | + | |
| - | [[Category: Atp-binding]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Mutant]]
| + | |
| - | [[Category: Nucleotide-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Receptor tyrosine kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| - | [[Category: Tyrosine-protein kinase]]
| + | |
| - | [[Category: Unphosphorylated]]
| + | |
| Structural highlights
Function
EPHB4_HUMAN Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation form EFNB2-expressing cells. Plays also a role in postnatal blood vessel remodeling, morphogenesis and permeability and is thus important in the context of tumor angiogenesis.[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
Crystallographic studies of a range of 3-substituted anilinopyrimidine inhibitors of EphB4 have highlighted two alternative C-2 aniline conformations and this discovery has been exploited in the design of a highly potent series of 3,5-disubstituted anilinopyrimidines. The observed range of cellular activities has been rationalised on the basis of physicochemical and structural characteristics.
Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines.,Bardelle C, Coleman T, Cross D, Davenport S, Kettle JG, Ko EJ, Leach AG, Mortlock A, Read J, Roberts NJ, Robins P, Williams EJ Bioorg Med Chem Lett. 2008 Nov 1;18(21):5717-21. Epub 2008 Sep 27. PMID:18851911[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fuller T, Korff T, Kilian A, Dandekar G, Augustin HG. Forward EphB4 signaling in endothelial cells controls cellular repulsion and segregation from ephrinB2 positive cells. J Cell Sci. 2003 Jun 15;116(Pt 12):2461-70. Epub 2003 May 6. PMID:12734395 doi:10.1242/jcs.00426
- ↑ Erber R, Eichelsbacher U, Powajbo V, Korn T, Djonov V, Lin J, Hammes HP, Grobholz R, Ullrich A, Vajkoczy P. EphB4 controls blood vascular morphogenesis during postnatal angiogenesis. EMBO J. 2006 Feb 8;25(3):628-41. Epub 2006 Jan 19. PMID:16424904 doi:10.1038/sj.emboj.7600949
- ↑ Bardelle C, Coleman T, Cross D, Davenport S, Kettle JG, Ko EJ, Leach AG, Mortlock A, Read J, Roberts NJ, Robins P, Williams EJ. Inhibitors of the tyrosine kinase EphB4. Part 2: structure-based discovery and optimisation of 3,5-bis substituted anilinopyrimidines. Bioorg Med Chem Lett. 2008 Nov 1;18(21):5717-21. Epub 2008 Sep 27. PMID:18851911 doi:10.1016/j.bmcl.2008.09.087
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