Determination of the kinetics of guanine nucleotide exchange on EF-Tu and EF-Ts: continuing uncertainties.
An analysis is made of the rate constants for the reactions involving the interactions of EF-Tu, EF-Ts, GDP, and GTP recently derived by Gromadski et al. [Biochemistry 41 (2002) 162]. Though their measured values appear to allow a reasonable rate of nucleotide exchange sufficient to support rates of protein synthesis in vivo, their data underestimate the thermodynamic barrier involved in nucleotide exchange and therefore cannot be considered definitive. A kinetic scheme consistent with the thermodynamic barrier can be achieved by modification of various rate constants, particularly of those involving the release of EF-Ts from EF-Tu.GTP.EF-Ts, but such constants are markedly different from what are experimentally observed. It thus remains impossible at present satisfactorily to model guanine nucleotide exchange on EF-Tu, catalysed by EF-Ts by a double displacement mechanism, with experimentally derived rate constants. Metabolic control analysis has been applied to determine the degree of flux control of the different steps in the pathway.
Manchester
Keith L
KL
School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa. kmanches@gecko.biol.wits.ac.za
D003198:Computer Simulation; D004734:Energy Metabolism / Q000502:physiology*; D004926:Escherichia coli / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D010444:Peptide Elongation Factor Tu / Q000378:metabolism*; D010445:Peptide Elongation Factors / Q000378:metabolism*; D011485:Protein Binding
D006150:Guanine Nucleotides; D010445:Peptide Elongation Factors; C023512:elongation factor Ts; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D010444:Peptide Elongation Factor Tu