CPK Color Scheme
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On this page, you can see the tyrosine kinase domain of the Epidermal Growth Factor Receptor with or without the 4-anilinoquinazoline inhibitor erlotinib. If you would like to learn more, or need a refresher on EGFR tyrosine kinase scroll down to the bottom and view some of the links.Jmol from PDB
Reset and spin the EGFR protein.
Look at the secondary structure of the tyrosine kinase domain. How many beta sheets (pink) are there? How about alpha helixes (orange)?
Look where Erlotinib (red) binds. Erlotinib is a tyrosine kinase inhibitor. It is used as a treatment for cancers that have an over-expression of EGFR. The over-expression causes rapid cell growth and differentiation. However, Erlotinib binds in the spot where ATP normally binds. As a result, Erlotinib prevents the phosphorylation of tyrosine residues. Thus, preventing the signal cascade from occurring.
In a EGFR tyrosine kinase domain, the tyrosine residues (yellow) are autophosphorylated, and the phosphorylation causes a signal cascade throughout the cell.
This white loop is called the activation loop. It is a conserved structure among EGFRs, and it requires phosphorylation for the kinase to become fully active.
Look at this molecule (yellow). This molecule is tyrosine 845. It is an important tyrosine residue as it stabilizes the activation loop and provides a binding surface for other proteins.
Can you tell what end of the protein leads to the carboxy-terminal tail? The juxtamembrane region? Hint: Wait. The carboxy-terminal tail has a tyrosine residue that is capable of being autophosphorylated.
Look at this threonine residue (silver). This amino acid is located in the beginning of the juxtamembrane region and it is capable of being phosphorylated by Protein Kinase C.
This residue (green) is leucine 790. It is an important residue as point mutations at this location are known to confer resistance to tyrosine kinase inhibitors like Erlotinib.
For Other Cool EGFR Information
Davidson College Molecular Biology