1xkk

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
[[Image:1xkk.gif|left|200px]]
[[Image:1xkk.gif|left|200px]]
-
{{Structure
+
<!--
-
|PDB= 1xkk |SIZE=350|CAPTION= <scene name='initialview01'>1xkk</scene>, resolution 2.40&Aring;
+
The line below this paragraph, containing "STRUCTURE_1xkk", creates the "Structure Box" on the page.
-
|SITE=
+
You may change the PDB parameter (which sets the PDB file loaded into the applet)
-
|LIGAND= <scene name='pdbligand=FMM:N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE'>FMM</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>
+
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] </span>
+
or leave the SCENE parameter empty for the default display.
-
|GENE= EGFR, ERBB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+
-->
-
|DOMAIN=
+
{{STRUCTURE_1xkk| PDB=1xkk | SCENE= }}
-
|RELATEDENTRY=
+
-
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xkk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xkk OCA], [http://www.ebi.ac.uk/pdbsum/1xkk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xkk RCSB]</span>
+
-
}}
+
'''EGFR kinase domain complexed with a quinazoline inhibitor- GW572016'''
'''EGFR kinase domain complexed with a quinazoline inhibitor- GW572016'''
Line 40: Line 37:
[[Category: Wood, E R.]]
[[Category: Wood, E R.]]
[[Category: Yuan, D.]]
[[Category: Yuan, D.]]
-
[[Category: egfr]]
+
[[Category: Egfr]]
-
[[Category: epidermal growth factor receptor]]
+
[[Category: Epidermal growth factor receptor]]
-
[[Category: kinase]]
+
[[Category: Kinase]]
-
 
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 15:08:44 2008''
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:50:54 2008''
+

Revision as of 12:08, 3 May 2008

Image:1xkk.gif

Template:STRUCTURE 1xkk

EGFR kinase domain complexed with a quinazoline inhibitor- GW572016


Overview

GW572016 (Lapatinib) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor (EGFR, ErbB-1) and ErbB-2. We determined the crystal structure of EGFR bound to GW572016. The compound is bound to an inactive-like conformation of EGFR that is very different from the active-like structure bound by the selective EGFR inhibitor OSI-774 (Tarceva) described previously. Surprisingly, we found that GW572016 has a very slow off-rate from the purified intracellular domains of EGFR and ErbB-2 compared with OSI-774 and another EGFR selective inhibitor, ZD-1839 (Iressa). Treatment of tumor cells with these inhibitors results in down-regulation of receptor tyrosine phosphorylation. We evaluated the duration of the drug effect after washing away free compound and found that the rate of recovery of receptor phosphorylation in the tumor cells reflected the inhibitor off-rate from the purified intracellular domain. The slow off-rate of GW572016 correlates with a prolonged down-regulation of receptor tyrosine phosphorylation in tumor cells. The differences in the off-rates of these drugs and the ability of GW572016 to inhibit ErbB-2 can be explained by the enzyme-inhibitor structures.

About this Structure

1XKK is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells., Wood ER, Truesdale AT, McDonald OB, Yuan D, Hassell A, Dickerson SH, Ellis B, Pennisi C, Horne E, Lackey K, Alligood KJ, Rusnak DW, Gilmer TM, Shewchuk L, Cancer Res. 2004 Sep 15;64(18):6652-9. PMID:15374980 Page seeded by OCA on Sat May 3 15:08:44 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1xkk"
Personal tools