2j5f

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[[Image:2j5f.jpg|left|200px]]<br /><applet load="2j5f" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2j5f.jpg|left|200px]]
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caption="2j5f, resolution 3.00&Aring;" />
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'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB'''<br />
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{{Structure
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|PDB= 2j5f |SIZE=350|CAPTION= <scene name='initialview01'>2j5f</scene>, resolution 3.00&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=DJK:N-[4-(3-BROMO-PHENYLAMINO)-QUINAZOLIN-6-YL]-ACRYLAMIDE'>DJK</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''CRYSTAL STRUCTURE OF EGFR KINASE DOMAIN IN COMPLEX WITH AN IRREVERSIBLE INHIBITOR 34-JAB'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2J5F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=DJK:'>DJK</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J5F OCA].
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2J5F is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J5F OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17334377 17334377]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/17334377 17334377]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Receptor protein-tyrosine kinase]]
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[[Category: wild-type]]
[[Category: wild-type]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:59:24 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:37:27 2008''

Revision as of 15:37, 20 March 2008

Image:2j5f.jpg


PDB ID 2j5f

Drag the structure with the mouse to rotate
, resolution 3.00Å
Ligands:
Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1
Coordinates: save as pdb, mmCIF, xml



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


Contents

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.

Disease

Known diseases associated with this structure: Adenocarcinoma of lung, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, response to tyrosine kinase inhibitor in OMIM:[131550], Nonsmall cell lung cancer, susceptibility to OMIM:[131550]

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

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