Copper ions as inhibitors of protein C of soluble methane monooxygenase of Methylococcus capsulatus (Bath).
Copper(I), copper(II) and silver ions have been shown to be potent inhibitors of purified soluble methane monooxygenase (MMO) of Methylococcus capsulatus (Bath). A weaker inhibition has been observed with zinc and cadmium ions. Proteins A and B of soluble MMO are unaffected by copper but protein C is rapidly and irreversibly inhibited. The site of copper inhibition has been shown to be primarily at the iron-sulphur centre of protein C with a secondary effect at the FAD centre when the copper(II):protein C ratio is high. Copper appears to bring about the inhibition of soluble MMO by interacting with protein C to disrupt the protein structure causing, firstly, the loss of the iron-sulphur centre, preventing the transfer of electrons from protein C to protein A, and secondly, the loss of FAD preventing the protein from accepting electrons from NADH. Inhibition and spectral data are provided to support this thesis. The inactivation of protein C is associated with the tight binding of four Cu atoms to each protein C molecule. These data extend our knowledge of how copper, which is known to have a key role in the cellular location of MMO, interacts with and rapidly and irreversibly inactivates the soluble form of this enzyme.
D001665:Binding Sites; D003300:Copper / Q000494:pharmacology*; D008670:Metals / Q000494:pharmacology; D008772:Methylococcaceae / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011487:Protein Conformation; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D008670:Metals; D009243:NAD; D003300:Copper; D010105:Oxygenases; C021555:methane monooxygenase