Showing papers by "Kavita Shah published in 1999"
TL;DR: The potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors and should allow the same complementary inhibitor/protein design strategy to be wideloaded into the kinase active sites.
Abstract: Selective protein kinase inhibitors are highly sought after as tools for studying cellular signal transduction cascades, yet few have been discovered due to the highly conserved fold of kinase catalytic domains. Through a combination of small molecule synthesis and protein mutagenesis, a highly potent (IC50 = 1.5 nM) and uniquely specific inhibitor (4-amino-1-tert-butyl-3-(1‘-naphthyl)pyrazolo[3,4-d]pyrimidine) of a rationally engineered v-Src tyrosine kinase (Ile338Gly v-Src) has been identified. Both the potency and specificity of this compound surpass those of any known Src family tyrosine kinase inhibitors. The molecule strongly inhibits the engineered v-Src in whole cells but does not inhibit tyrosine phosphorylation in cells that express only wild-type tyrosine kinases. In addition, the inhibitor selectively disrupts transformation in cells that express the target v-Src. The structural degeneracy of kinase active sites should allow the same complementary inhibitor/protein design strategy to be widel...
191 citations
TL;DR: A mutation in myosin's nucleotide-binding pocket that permits binding of adenine nucleotides modified with bulky N 6substituents is designed and introduced, which did not alter the enzyme's affinity for ATP or actin and actually increased its ATPase activity and actin-translocation rate.
76 citations