Catalysis of guanine nucleotide exchange on eIF2 by eIF2B: can it be both a substituted enzyme and a sequential mechanism?

There are conflicting reports over the question of whether the displacement by GTP of GDP bound to eIF2 catalyzed by eIF2B follows a substituted enzyme mechanism, as is believed to be the case for other guanine nucleotide exchange factors, or is a sequential mechanism. Analysis of data recently provided by Williams et al. (J. Biol. Chem. 276, 24697-24703, 2001) showing displacement by eIF2B of GDP bound to eIF2 in the absence of displacing nucleotide appears to offer a way of resolving the dispute and suggests that both mechanisms may be operative. (c) 2001 Elsevier Science.