The effect of kirromycin on the metal ion coordination in complexes of elongation factor Tu from Bacillus stearothermophilus as inferred from the 17O-55Mn superhyperfine interaction.
The binding of the antibiotic kirromycin to elongation factor Tu (EF-Tu) leads to a severe line broadening of the Q-band manganese EPR lines of EF-Tu.Mn, EF-Tu.Mn.GDP, as well as EF-Tu.Mn.GDP.Pi indicating that the coordination sphere of the metal ion is changed by this interaction. The number of coordinated water molecules was determined from the 17O-55Mn superhyperfine coupling observable in H2(17)O enriched water; it is pH-dependent in the EF-Tu.Mn.GDP complex, at pH 6.8 probably four water molecules are coordinated with the protein bound manganese, at pH 8.4 one of the water molecules is replaced by a functional group from the protein. Independent of the pH, probably four and five water molecules are bound to the metal ion in the EF-Tu.Mn and in the EF-Tu.Mn.GDP.Pi complex, respectively. Kirromycin does not influence the number of water molecules bound to EF-Tu.Mn.GDP and EF-Tu.Mn.GDP.Pi, but leads to an increase of the number of water molecules coordinated to the metal ion in EF-Tu.Mn. The 17O-55Mn superhyperfine coupling constant in Mn(H2O)6 was determined from the EPR-spectra as 0.24 mT.
Kalbitzer
H R
HR
Max-Planck-Institute for Medical Research, Department of Biophysics, Heidelberg, F.R.G.
Wittinghofer
A
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D001411:Geobacillus stearothermophilus / Q000187:drug effects* / Q000378:metabolism; D008345:Manganese / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010444:Peptide Elongation Factor Tu / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008670:Metals; D011728:Pyridones; D008345:Manganese; D010444:Peptide Elongation Factor Tu; C008536:mocimycin; D010100:Oxygen