Abstract:
:A model protein, ribonuclease A (bovine pancreas), was examined for its ability to coordinate Ni2+ and promote selective oxidation. In the presence of a peracid such as monopersulfate, HSO5-, nickel induced the monomeric RNase A to form dimers, trimers, tetramers, and higher oligomers without producing fragmentation of the polypeptide backbone. Co2+ and to a lesser extent Cu2+ exhibited similar activity. The nickel-dependent reaction appeared to result from a specific association between the protein and Ni2+ that allowed for transient and in situ oxidation of the bound nickel to yield intermolecular tyrosine-tyrosine cross-links. Macrocylic nickel complexes that had previously been shown to promote guanine oxidation were unable to mimic the activity of the free metal salt. Amino acid analysis of the protein dimer confirmed the expected consumption of one tyrosine per polypeptide and formation of dityrosine. The presence of excess tyrosine efficiently inhibited formation of the protein dimer and produced instead a ribonuclease-tyrosine cross-link. In contrast, high concentrations of the hydroxyl radical quenching agent mannitol only partially inhibited ribonuclease dimerization. The polypeptide-mediated activation of nickel and its subsequent reactivity mimic a process that could contribute to the adverse effects of nickel in vivo.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Gill G,Richter-Rusli AA,Ghosh M,Burrows CJ,Rokita SEdoi
10.1021/tx960170isubject
Has Abstractpub_date
1997-03-01 00:00:00pages
302-9issue
3eissn
0893-228Xissn
1520-5010pii
tx960170ijournal_volume
10pub_type
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