2j5f

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[[Image:2j5f.jpg|left|200px]]
[[Image:2j5f.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2j5f |SIZE=350|CAPTION= <scene name='initialview01'>2j5f</scene>, resolution 3.00&Aring;
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The line below this paragraph, containing "STRUCTURE_2j5f", creates the "Structure Box" on the page.
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|SITE=
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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=DJK:N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE'>DJK</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/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>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2j5f| PDB=2j5f | 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=2j5f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j5f OCA], [http://www.ebi.ac.uk/pdbsum/2j5f PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j5f RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB'''
'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB'''
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[[Category: Yun, C H.]]
[[Category: Yun, C H.]]
[[Category: 34-jab]]
[[Category: 34-jab]]
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[[Category: alternative splicing]]
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[[Category: Alternative splicing]]
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[[Category: anti-oncogene]]
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[[Category: Anti-oncogene]]
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[[Category: atp-binding]]
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[[Category: Atp-binding]]
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[[Category: cell cycle]]
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[[Category: Cell cycle]]
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[[Category: disease mutation]]
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[[Category: Disease mutation]]
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[[Category: egfr]]
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[[Category: Egfr]]
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[[Category: epidermal growth factor]]
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[[Category: Epidermal growth factor]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: irreversible inhibitor]]
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[[Category: Irreversible inhibitor]]
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[[Category: kinase]]
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[[Category: Kinase]]
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[[Category: membrane]]
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[[Category: Membrane]]
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[[Category: nucleotide-binding]]
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[[Category: Nucleotide-binding]]
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[[Category: phosphorylation]]
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[[Category: Phosphorylation]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: receptor]]
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[[Category: Receptor]]
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[[Category: transferase]]
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[[Category: Transferase]]
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[[Category: transmembrane]]
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[[Category: Transmembrane]]
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[[Category: tyrosine-protein kinase]]
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[[Category: Tyrosine-protein kinase]]
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[[Category: ubl conjugation]]
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[[Category: Ubl conjugation]]
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[[Category: wild-type]]
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[[Category: Wild-type]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 08:21:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:53:12 2008''
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Revision as of 05:21, 4 May 2008

Image:2j5f.jpg

Template:STRUCTURE 2j5f

CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB


Overview

As key components in nearly every signal transduction pathway, protein kinases are attractive targets for the regulation of cellular signaling by small-molecule inhibitors. We report the structure-guided development of 6-acrylamido-4-anilinoquinazoline irreversible kinase inhibitors that potently and selectively target rationally designed kinases bearing two selectivity elements that are not found together in any wild-type kinase: an electrophile-targeted cysteine residue and a glycine gatekeeper residue. Cocrystal structures of two irreversible quinazoline inhibitors bound to either epidermal growth factor receptor (EGFR) or engineered c-Src show covalent inhibitor binding to the targeted cysteine (Cys797 in EGFR and Cys345 in engineered c-Src). To accommodate the new covalent bond, the quinazoline core adopts positions that are different from those seen in kinase structures with reversible quinazoline inhibitors. Based on these structures, we developed a fluorescent 6-acrylamido-4-anilinoquinazoline affinity probe to report the fraction of kinase necessary for cellular signaling, and we used these reagents to quantitate the relationship between EGFR stimulation by EGF and its downstream outputs-Akt, Erk1 and Erk2.

About this Structure

2J5F is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure-guided development of affinity probes for tyrosine kinases using chemical genetics., Blair JA, Rauh D, Kung C, Yun CH, Fan QW, Rode H, Zhang C, Eck MJ, Weiss WA, Shokat KM, Nat Chem Biol. 2007 Apr;3(4):229-38. Epub 2007 Mar 4. PMID:17334377 Page seeded by OCA on Sun May 4 08:21:45 2008

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