Conformational ensemble modulates cooperativity in the rate-determining catalytic step in the E1 component of the Escherichia coli pyruvate dehydrogenase multienzyme complex.

ABSTRACT: Cooperativity is extensively used by enzymes, particularly those acting at key metabolic branch points, to "fine tune" catalysis. Thus, cooperativity and enzyme catalysis are intimately linked, yet their linkage is poorly understood. Here we show that negative cooperativity in the rate-determining step in the E1 component of the Escherichia coli pyruvate dehydrogenase multienzyme complex is an outcome of redistribution of a "rate-promoting" conformational pre-equilibrium. An array of biophysical and biochemical studies indicates that non-catalytic but conserved residues directly regulate the redistribution. Furthermore, factors such as ligands and temperature, individually or in concert, also strongly influence the redistribution. As a consequence, these factors also exert their influence

SUBMITTER: Kale S 

PROVIDER: S-EPMC2785154 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature