| Popis: |
Progress towards understanding catalytically 'dead' protein kinases - pseudokinases - in biology and disease has hastened over the past decade. An especially lively area for structural biology, pseudokinases appear to be strikingly similar to their kinase relatives, despite lacking key catalytic residues. Distinct active- and inactive-like conformation states, which are crucial for regulating bona fide protein kinases, are conserved in pseudokinases and appear to be essential for function. We discuss recent structural data on conformational transitions and nucleotide binding by pseudokinases, from which some common principles emerge. In both pseudokinases and bona fide kinases, a conformational toggle appears to control the ability to interact with signaling effectors. We also discuss how biasing this conformational toggle may provide opportunities to target pseudokinases pharmacologically in disease. |
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