1yy8: Difference between revisions

Revision as of 16:29, 20 March 2008

, resolution 2.00Å

Coordinates:

Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225

OverviewOverview

Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation.

About this StructureAbout this Structure

1YY8 is a Protein complex structure of sequences from Mus musculus/homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for inhibition of the epidermal growth factor receptor by cetuximab., Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM, Cancer Cell. 2005 Apr;7(4):301-11. PMID:15837620

Page seeded by OCA on Thu Mar 20 15:28:59 2008

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OCA

@@ Line 1: / Line 1: @@
-[[Image:1yy8.gif|left|200px]]<br /><applet load="1yy8" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1yy8.gif|left|200px]]
-caption="1yy8, resolution 2.00&Aring;" />
-'''Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225'''<br />
+ {{Structure
+|PDB= 1yy8 |SIZE=350|CAPTION= <scene name='initialview01'>1yy8</scene>, resolution 2.00&Aring;
+|SITE=
+|LIGAND=
+|ACTIVITY=
+|GENE=
+}}
+'''Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-YY8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus/homo_sapiens Mus musculus/homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YY8 OCA].
+YY8 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus/homo_sapiens Mus musculus/homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YY8 OCA].
 ==Reference==
-Structural basis for inhibition of the epidermal growth factor receptor by cetuximab., Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM, Cancer Cell. 2005 Apr;7(4):301-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15837620 15837620]
+Structural basis for inhibition of the epidermal growth factor receptor by cetuximab., Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM, Cancer Cell. 2005 Apr;7(4):301-11. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15837620 15837620]
 [[Category: Mus musculus/homo sapiens]]
 [[Category: Protein complex]]
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 [[Category: fab fragment; antibody drug; cancer]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:20 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:28:59 2008''