4p4c: Difference between revisions

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'''Unreleased structure'''
==Human EphA3 Kinase domain in complex with quinoxaline derivatives==
<StructureSection load='4p4c' size='340' side='right' caption='[[4p4c]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4p4c]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P4C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P4C FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=25Q:2-AMINO-1-(3-METHOXYPHENYL)-1H-PYRROLO[2,3-B]QUINOXALINE-3-CARBOXAMIDE'>25Q</scene><br>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p4c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p4c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p4c RCSB], [http://www.ebi.ac.uk/pdbsum/4p4c PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The X-ray crystal structures of the catalytic domain of the EphA3 tyrosine kinase in complex with two type I inhibitors previously discovered in silico (compounds A and B) were used to design type I1/2 and II inhibitors. Chemical synthesis of about 25 derivatives culminated in the discovery of compounds 11d (type I1/2), 7b, and 7g (both of type II), which have low-nanomolar affinity for Eph kinases in vitro and a good selectivity profile on a panel of 453 human kinases (395 nonmutant). Surface plasmon resonance measurements show a very slow unbinding rate (1/115 min) for inhibitor 7m. Slow dissociation is consistent with a type II binding mode in which the hydrophobic moiety (trifluoromethyl-benzene) of the inhibitor is deeply buried in a cavity originating from the displacement of the Phe side chain of the so-called DFG motif as observed in the crystal structure of compound 7m. The inhibitor 11d displayed good in vivo efficacy in a human breast cancer xenograft.


The entry 4p4c is ON HOLD  until Paper Publication
Pyrrolo[3,2-b]quinoxaline Derivatives as Types I and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation.,Unzue A, Dong J, Lafleur K, Zhao H, Frugier E, Caflisch A, Nevado C J Med Chem. 2014 Jul 30. PMID:25076195<ref>PMID:25076195</ref>


Authors: Dong, J., Caflisch, A.
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 
</div>
Description: Human EphA3 Kinase domain in complex with quinoxaline derivatives
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Caflisch, A.]]
[[Category: Dong, J.]]
[[Category: Transferase-transferase inhibitor complex]]
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