Comparison of the Tu elongation factors from Staphylococcus aureus and Escherichia coli: possible basis for elfamycin insensitivity.
In a previous study (C. C. Hall, J. D. Watkins, and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:322-325, 1989), the elongation factor Tu (EF-Tu) from Staphylococcus aureus was found to be insensitive to a series of kirromycin analogs which were inhibitory to the EF-Tu from Escherichia coli. In the present study, the EF-Tu from S. aureus was partially purified and characterized. Its apparent molecular mass was approximately 41,000 Da, and the enzyme copurified with EF-Ts (molecular mass, 34,000 Da). S. aureus EF-Tu differed from its E. coli counterpart in that it bound negligible amounts of [3H]GDP, in addition to being insensitive to pulvomycin and aurodox (50% inhibitory concentrations, approximately 100 and 1,000 microM, respectively, versus 2 and 0.2 microM, respectively, for E. coli). The results are consistent with the formation of a stable EF-Tu.EF-Ts complex that affects the interaction of EF-Tu with guanine nucleotides and inhibitors.
Hall
C C
CC
Roche Research Center, Nutley, New Jersey 07110.
Watkins
J D
JD
Georgopapadakou
N H
NH
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000899:Aurodox / Q000031:analogs & derivatives* / Q000494:pharmacology; D002848:Chromatography, DEAE-Cellulose; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008970:Molecular Weight; D010452:Peptide Biosynthesis; D010444:Peptide Elongation Factor Tu / Q000187:drug effects* / Q000302:isolation & purification; D010455:Peptides; D011728:Pyridones / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010455:Peptides; D011728:Pyridones; C012521:pulvomycin; D000899:Aurodox; D006153:Guanosine Diphosphate; C012001:polyphenylalanine; C012954:efrotomycin; D006160:Guanosine Triphosphate; D000251:Adenosine Triphosphatases; D010444:Peptide Elongation Factor Tu; C008536:mocimycin