THE ALLOSTERIC REGULATION OF PYRUVATE-KINASE

Crystallographic and mutagenesis studies have unravelled the general f eatures of the allosteric transition mechanism in pyruvate kinase, The enzyme displays a dramatic conformational change in going from the T- to the R-state, All three domains forming each subunit of the tetrame ric enzyme undergo simultaneous and concerted rotations, in such a way that all subunit and domain interfaces are modified, This mechanism i s unprecedented since in all tetrameric allosteric enzymes, characteri sed at atomic resolution, at least one of the domain or subunit interf aces remains unchanged on the T- to R-state transition, The molecular mechanism of allosteric regulation here proposed provides a rationale for the effect of single site mutations observed in the human erythroc yte pyruvate kinase associated with a congenital anaemia.