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| | <StructureSection load='2vwu' size='340' side='right'caption='[[2vwu]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2vwu' size='340' side='right'caption='[[2vwu]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vwu]] 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=2VWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VWU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vwu]] 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=2VWU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VWU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7X1:N-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-6-METHOXY-7-(3-PIPERIDIN-1-YLPROPOXY)QUINAZOLIN-4-AMINE'>7X1</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]] 2Å</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]], [[2vwv|2vwv]], [[2vwy|2vwy]], [[2vww|2vww]], [[2vwx|2vwx]], [[2vwz|2vwz]], [[2vx0|2vx0]], [[2vx1|2vx1]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7X1:N-(5-CHLORO-1,3-BENZODIOXOL-4-YL)-6-METHOXY-7-(3-PIPERIDIN-1-YLPROPOXY)QUINAZOLIN-4-AMINE'>7X1</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=2vwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vwu OCA], [https://pdbe.org/2vwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vwu RCSB], [https://www.ebi.ac.uk/pdbsum/2vwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vwu 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=2vwu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vwu OCA], [https://pdbe.org/2vwu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vwu RCSB], [https://www.ebi.ac.uk/pdbsum/2vwu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vwu 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: McAlister M]] |
| - | [[Category: McAlister, M]] | + | [[Category: McCall EJ]] |
| - | [[Category: McCall, E J]] | + | [[Category: Packer M]] |
| - | [[Category: Packer, M]] | + | [[Category: Read J]] |
| - | [[Category: Read, J]] | + | [[Category: Rowsell S]] |
| - | [[Category: Rowsell, S]] | + | [[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
A series of bis-anilinopyrimidines have been identified as potent inhibitors of the tyrosine kinase EphB4. Structural information from two alternative series identified from screening efforts was combined to identify the initial leads.
Inhibitors of the tyrosine kinase EphB4. Part 1: Structure-based design and optimization of a series of 2,4-bis-anilinopyrimidines.,Bardelle C, 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 May 1;18(9):2776-80. Epub 2008 Apr 10. PMID:18434142[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, 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 1: Structure-based design and optimization of a series of 2,4-bis-anilinopyrimidines. Bioorg Med Chem Lett. 2008 May 1;18(9):2776-80. Epub 2008 Apr 10. PMID:18434142 doi:10.1016/j.bmcl.2008.04.015
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