2qi8

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[[Image:2qi8.jpg|left|200px]]
[[Image:2qi8.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2qi8 |SIZE=350|CAPTION= <scene name='initialview01'>2qi8</scene>, resolution 2.320&Aring;
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The line below this paragraph, containing "STRUCTURE_2qi8", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Residue+A+100'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= SRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 Gallus gallus])
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-->
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|DOMAIN=
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{{STRUCTURE_2qi8| PDB=2qi8 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qi8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qi8 OCA], [http://www.ebi.ac.uk/pdbsum/2qi8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qi8 RCSB]</span>
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}}
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'''Crystal structure of drug resistant SRC kinase domain'''
'''Crystal structure of drug resistant SRC kinase domain'''
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[[Category: Rauh, D.]]
[[Category: Rauh, D.]]
[[Category: Rode, H B.]]
[[Category: Rode, H B.]]
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[[Category: drug resistance]]
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[[Category: Drug resistance]]
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[[Category: signaling protein]]
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[[Category: Signaling protein]]
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[[Category: src kinase domain]]
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[[Category: Src kinase domain]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 15:00:31 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:49:32 2008''
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Revision as of 12:00, 4 May 2008

Image:2qi8.jpg

Template:STRUCTURE 2qi8

Crystal structure of drug resistant SRC kinase domain


Overview

Resistance to kinase- targeted cancer drugs has recently been linked to a single point mutation in the ATP binding site of the kinase. In EGFR, the crucial Thr790 gatekeeper residue is mutated to a Met and prevents reversible ATP competitive inhibitors from binding. Irreversible 4-(phenylamino)quinazolines have been shown to overcome this drug resistance and are currently in clinical trials. In order to obtain a detailed structural understanding of how irreversible inhibitors overcome drug resistance, we used Src kinase as a model system for drug resistant EGFR-T790M. We report the first crystal structure of a drug resistant kinase in complex with an irreversible inhibitor. This 4-(phenylamino)quinazoline inhibits wild type and drug resistant EGFR in vitro at low nM concentrations. The co-crystal structure of drug resistant cSrc-T338M kinase domain provides the structural basis of this activity.

About this Structure

2QI8 is a Single protein structure of sequence from Gallus gallus. Full crystallographic information is available from OCA.

Reference

Structural insights into how irreversible inhibitors can overcome drug resistance in EGFR., Michalczyk A, Kluter S, Rode HB, Simard JR, Grutter C, Rabiller M, Rauh D, Bioorg Med Chem. 2008 Feb 20;. PMID:18316192 Page seeded by OCA on Sun May 4 15:00:31 2008

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