4g2f: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4g2f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G2F FirstGlance]. <br> | <table><tr><td colspan='2'>[[4g2f]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G2F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4G2F FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C07:1-AMINO-5-(5-HYDROXY-2-METHYLPHENYL)-7,8,9,10-TETRAHYDROPYRIMIDO[4,5-C]ISOQUINOLIN-6(5H)-ONE'>C07</scene>< | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C07:1-AMINO-5-(5-HYDROXY-2-METHYLPHENYL)-7,8,9,10-TETRAHYDROPYRIMIDO[4,5-C]ISOQUINOLIN-6(5H)-ONE'>C07</scene></td></tr> | ||
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPHA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EPHA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<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 id='activity'><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=4g2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g2f RCSB], [http://www.ebi.ac.uk/pdbsum/4g2f PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4g2f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g2f OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4g2f RCSB], [http://www.ebi.ac.uk/pdbsum/4g2f PDBsum]</span></td></tr> | ||
<table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 25: | Line 25: | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Caflisch, A | [[Category: Caflisch, A]] | ||
[[Category: Dong, J | [[Category: Dong, J]] | ||
[[Category: Atp binding]] | [[Category: Atp binding]] | ||
[[Category: Membrane]] | [[Category: Membrane]] | ||
Revision as of 15:33, 5 January 2015
Human EphA3 kinase domain in complex with compound 7Human EphA3 kinase domain in complex with compound 7
Structural highlights
Publication Abstract from PubMedWe have discovered a novel chemical class of inhibitors of the EphB4 tyrosine kinase by fragment-based high-throughput docking followed by explicit solvent molecular dynamics simulations for assessment of the binding mode. The synthesis of a single derivative (compound 7) of the hit identified in silico has resulted in an improvement of the inhibitory potency in an enzymatic assay from 8.4 muM to 160 nM and a ligand efficiency of 0.39 kcal/mol per non-hydrogen atom. Such remarkable improvement in affinity is due to an additional hydroxyl group involved in two favorable (buried) hydrogen bonds as predicted by molecular dynamics and validated by the crystal structure of the complex with EphA3 solved at 1.7 A resolution. Discovery of a novel chemotype of tyrosine kinase inhibitors by fragment-based docking and molecular dynamics.,Zhao H, Dong J, Lafleur K, Nevado C, Caflisch A ACS Med Chem Lett. 2012 Aug 23;3(10):834-8. doi: 10.1021/ml3001984. eCollection, 2012 Oct 11. PMID:24900387[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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