Citation | Laurence Pearl has applied structural, biochemical and genetic techniques, to elucidate the molecular basis of function and specificity in systems of fundamental biomedical importance. His pioneering work on retroviral proteases was a key step in the recognition of HIV protease as a therapeutic target in AIDS. He has made seminal contributions to our understanding of the recognition and repair of DNA damage. In studies of the molecular chaperone Hsp90, he was the first to show its function depended on binding and hydrolysis of ATP, and he defined the mechanism of the ATPase-coupled molecular clamp that drives the chaperone cycle. In his research on cell signalling he has determined the structure of GSK3-beta, showing how it recognises substates, and elucidating how it is inhibited through insulin signalling. |