Computational delineation of tyrosyl-substrate recognition and catalytic landscapes by the epidermal growth factor receptor tyrosine kinase domain.

ABSTRACT: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK), which catalyzes protein phosphorylation reactions by transferring the γ-phosphoryl group from an ATP molecule to the hydroxyl group of tyrosine residues in protein substrates. EGFR is an important drug target in the treatment of cancers and a better understanding of the receptor function is critical to discern cancer mechanisms. We employ a suite of molecular simulation methods to explore the mechanism of substrate recognition and to delineate the catalytic landscape of the phosphoryl transfer reaction. Based on our results, we propose that a highly conserved region corresponding to Val852-Pro853-Ile854-Lys855-Trp856 in the EGFR tyrosine kinase domain (TKD) is essential for substrate binding. We also provide a

SUBMITTER: Liu Y 

PROVIDER: S-EPMC4074314 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature