Kinetic modelling of the effect of alpha subunit phosphorylation on the activity of the protein synthesis initiation factor eIF-2.
The ability of eIF-2.GDP in which the alpha subunit of eIF-2 is phosphorylated (eIF-2(alpha P).GDP) to act as a competitive inhibitor of eIF-2B-catalysed exchange of eIF-2-bound GDP has been investigated by modelling data provided by Rowlands et al. (J. Biol. Chem. 263, 5526-5533:1988). Some revision of previously determined dissociation and rate constants proved to be necessary. Under the conditions employed it was not possible to demonstrate significant inhibition of GDP exchange by eIF-2 (alpha P).GDP without substantial increase in its affinity for eIF-2B over that of eIF-2.GDP. Classic double reciprocal plots for competitive inhibition were found only when [eIF-2B] was low in relation to [eIF-2 (alpha P).GDP]. Relatively high cellular [eIF-2B] lessens the inhibitory effect of eIF-2(alpha P).GDP and suggests the possibility of other potential controls of initiation.
Manchester
K L
KL
Department of Biochemistry, University of the Witwatersrand, Johannesburg, South Africa.
D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000037:antagonists & inhibitors; D007700:Kinetics; D008954:Models, Biological; D010766:Phosphorylation; D011485:Protein Binding; D013696:Temperature
D015852:Eukaryotic Initiation Factor-2; D006153:Guanosine Diphosphate