Activities of guanosine triphosphate analogues in reactions catalyzed by elongation factor Tu and initiation factor 2 of Escherichia coli.
In earlier studies two natural analogues of GTP, guanosine 3'-diphosphate 5'-triphosphate (pppGpp) and dGTP, were found to substitute for GTP in reactions catalyzed by initiation factor 2 (IF-2) and elongation factor Tu (EF-Tu), while only dGTP could replace GTP with elongation factor G. These observations with IF-2 and EF-Tu have been extended to two analogues of GTP modified at the 3' ribose hydroxyl position, 3'-deoxyguanosine 5'-triphosphate (3'dGTP) and 3'-deoxy-3'-aminoguanosine 5'-triphosphate (3'dNH2GTP). These compounds were found to be similar to GTP, dGTP, and pppGpp in IF-2-dependent formation of N-formylmethionyl-puromycin and EF-Tu-dependent formation of N-acetyl-Phe-Phe-tRNA. The apparent Km values for the five guanosine nucleotides were 2 - 10(-6)-4 - 10(-6)M in the former reaction and 2-10(-7)--6-10(-7) M in the latter. These reactions did not have an absolute requirement for either an intact pentose ring or for the guanine base in the nucleotide. Although substantially less active than the guanine nucleotides, ITP and the dialcohol derived from GTP by periodate oxidation and borohydride reduction (ox-redGTP) were partially active in both the IF-2 and EF-Tu-dependent reactions, with apparent Km values about 40-100 times those of GTP.
D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007292:Inosine Nucleotides / Q000494:pharmacology; D007700:Kinetics; D010084:Oxidation-Reduction; D010441:Peptide Chain Elongation, Translational / Q000187:drug effects; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors
D006150:Guanine Nucleotides; D007292:Inosine Nucleotides; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D006160:Guanosine Triphosphate