In living cells, protein kinases are organized in large signalling complexes comprising adapter proteins, diverse enzymes and regulatory proteins. In recent years it has become increasingly evident, that protein kinases act not only as independent enzymes but that they also function as protein interaction scaffolds organizing the assembly of signalling complexes in a conformation sensitive way. This complexity is also reflected by the response of kinases to inhibitors that may stabilize diverse conformations acting as inhibitors of enzymatic activity only, as modulators of kinase scaffolding roles or both. In this talk, I will exemplify the implications of altering protein interactions by allosteric small molecules as well as canonical ATP competitive inhibitors using a number of selective inhibitors that we developed recently. I will demonstrate how different binding modes that alter protein conformation and dynamics in a distinct way may result in diverse signalling outcomes and phenotypic responses. The important scaffolding roles of protein kinases will also enable targeting new and so far poorly explored members of the kinase family such as catalytically inactive pseudokinases, that represent a considerable number of largely unexplored kinase targets which have been linked to the development of many diseases.
16 Luglio 2021
Prof. Dr. Stefan Knapp
Johann Wolfgang Goethe-University
Institute for Pharmaceutical Chemistry Frankfurt am Main, Germany.
Johann Wolfgang Goethe-University, Structural Genomics Consortium, Buchmann Institute for Life Sciences Frankfurt am Main, Germany.
Ore: 11:00 link: meet.google.com/ngf-bmpv-rdi
Email: knapp@pharmchem.uni-frankfurt.de
Il Professor Knapp resta a vostra disposizione per incontri e discussioni su eventuali argomenti di comune interesse scientifico (anche prima del seminario).