4HJO

Crystal structure of the inactive EGFR tyrosine kinase domain with erlotinib

Summary for 4HJO

• Entry DOI: 10.2210/pdb4hjo/pdb
• Descriptor: Epidermal growth factor receptor, [6,7-BIS(2-METHOXY-ETHOXY)QUINAZOLINE-4-YL]-(3-ETHYNYLPHENYL)AMINE (3 entities in total)
• Functional Keywords: inactive tyrosine kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted: P00533
• Total number of polymer chains: 1
• Total formula weight: 38950.01

Authors

Park, J.H.,Lemmon, M.A. (deposition date: 2012-10-13, release date: 2012-11-14, Last modification date: 2023-09-20)

Primary citation

Park, J.H.,Liu, Y.,Lemmon, M.A.,Radhakrishnan, R.
Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain.
Biochem.J., 448:417-423, 2012

PubMed Abstract: Erlotinib and gefitinib, tyrosine kinase inhibitors used to block EGFR (epidermal growth factor receptor) signalling in cancer, are thought to bind only the active conformation of the EGFR-TKD (tyrosine kinase domain). Through parallel computational and crystallographic studies, we show in the present study that erlotinib also binds the inactive EGFR-TKD conformation, which may have significant implications for its use in EGFR-mutated cancers.

PubMed: 23101586
DOI: 10.1042/BJ20121513

Experimental method

X-RAY DIFFRACTION (2.75 Å)