Citation | Robin Carrell is distinguished principally for studies on serpins. Carrell and colleagues have solved more than twenty serpin structures; elucidated their 'mousetrap' mechanism of action at a molecular level; and demonstrated the central importance of the binding site amino acid for the specificity of enzyme inhibition. An outstanding contribution has been to show that mutations in serpins alter their stability and cause polymerisation by the "reactive loop into beta-sheet" mechanism, giving rise to "conformational diseases". These include a familial dementia due to polymerisation of a neuroserpin. Recent success in identifying peptides that inhibit polymerisation should lead to rational therapies. |