1yy9
From Proteopedia
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Structure of the extracellular domain of the epidermal growth factor receptor in complex with the Fab fragment of cetuximab/Erbitux/IMC-C225
Contents |
Overview
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.
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
1YY9 is a Single protein structure of sequence from Homo sapiens and Mus musculus/homo sapiens with NDG and NAG as ligands. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from 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:15837620
Page seeded by OCA on Mon Nov 12 20:26:46 2007
