4aw5

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Current revision (07:16, 1 May 2024) (edit) (undo)
 
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<StructureSection load='4aw5' size='340' side='right'caption='[[4aw5]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
<StructureSection load='4aw5' size='340' side='right'caption='[[4aw5]], [[Resolution|resolution]] 2.33&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4aw5]] 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=4AW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AW5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4aw5]] 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=4AW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AW5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30K:(3Z)-5-[(1-ETHYLPIPERIDIN-4-YL)AMINO]-3-[(5-METHOXY-1H-BENZIMIDAZOL-2-YL)(PHENYL)METHYLIDENE]-1,3-DIHYDRO-2H-INDOL-2-ONE'>30K</scene></td></tr>
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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]] 2.33&#8491;</td></tr>
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<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]], [[2vww|2vww]], [[2vwx|2vwx]], [[2vwy|2vwy]], [[2vwz|2vwz]], [[2vx0|2vx0]], [[2vx1|2vx1]], [[2x9f|2x9f]], [[2xvd|2xvd]]</div></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=30K:(3Z)-5-[(1-ETHYLPIPERIDIN-4-YL)AMINO]-3-[(5-METHOXY-1H-BENZIMIDAZOL-2-YL)(PHENYL)METHYLIDENE]-1,3-DIHYDRO-2H-INDOL-2-ONE'>30K</scene></td></tr>
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<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>
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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=4aw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw5 OCA], [https://pdbe.org/4aw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aw5 RCSB], [https://www.ebi.ac.uk/pdbsum/4aw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aw5 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=4aw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4aw5 OCA], [https://pdbe.org/4aw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4aw5 RCSB], [https://www.ebi.ac.uk/pdbsum/4aw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4aw5 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[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>
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Variously substituted indolin-2-ones were synthesized and evaluated for activity against KDR, Flt-1, FGFR-1 and PDGFR. Extension at the 5-position of the oxindole ring with ethyl piperidine (compound 7i) proved to be the most beneficial for attaining both biochemical and cellular potencies. Further optimization of 7i to balance biochemical and cellular potencies with favorable ADME/ PK properties led to the identification of 8h, a compound with a clean CYP profile, acceptable pharmacokinetic and toxicity profiles, and robust efficacy in multiple xenograft tumor models.
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The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors.,Kim MH, Tsuhako AL, Co EW, Aftab DT, Bentzien F, Chen J, Cheng W, Engst S, Goon L, Klein RR, Le DT, Mac M, Parks JJ, Qian F, Rodriquez M, Stout TJ, Till JH, Won KA, Wu X, Michael Yakes F, Yu P, Zhang W, Zhao Y, Lamb P, Nuss JM, Xu W Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85. Epub 2012 Jun 16. PMID:22765894<ref>PMID:22765894</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 4aw5" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Human]]
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[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Stout TJ]]
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[[Category: Stout, T J]]
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[[Category: Till JH]]
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[[Category: Till, J H]]
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[[Category: Transferase]]
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Current revision

Complex of the EphB4 kinase domain with an oxindole inhibitor

PDB ID 4aw5

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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