Structural characterization of tyrosine kinase substrate binding and array-based functional peptide screening of Src kinase

Abstract

Protein kinases are a highly targeted class of enzymes for cancer therapeutics. All current FDA approved drugs bind within the ATP site and many demonstrate toxicity due to off-target effects. A new avenue is to design drugs that compete with substrate interactions. This requires the knowledge of how kinases interact with their substrates. Current structure information on kinase-substrate interactions is particularly deficient due to the transient nature of tyrosine kinase-substrate complexes. To overcome this deficiency, we are using NMR approaches and the native solution state to characterize structural patterns for substrate binding of Src tyrosine kinase, a well-known cancer-related drug target.