980-21-2Relevant articles and documents
Nickel-dependent oxidative cross-linking of a protein
Gill, Gurpreet,Richter-Rusli, Angelika A.,Ghosh, Madhushree,Burrows, Cynthia J.,Rokita, Steven E.
, p. 302 - 309 (1997)
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.
Synthesis, Ligand Binding and Biomimetic Oxidations of Deuterohaemin modified with an Undecapeptide Residue
Casella, Luigi,Gullotti, Michele,Gioia, Luca De,Monzani, Enrico,Chillemi, Francesco
, p. 2945 - 2954 (2007/10/02)
Deuterohaemin has been covalently linked to the undecapeptide Ala-Phe-Ser-Phe-Glu-Ala-Gln-Gly-Gly-Leu-Ala at one of the propionic acid side chains.The binding equilibria between the resulting deuterohaemin-undecapeptide complex and imidazole occur in two steps; the first molecule of the ligand binds with high affinity (K1 = 1500 dm3 mol-1), while for the second molecule the affinity is markedly lower (K2 = 220 dm3 mol-1), indicating that folding of the peptide chain in the monoimidazole adduct severely limits the accessibility of the sixth iron co-ordination position.The complex exhibits both catalase and peroxidase activity towards reducing substrates in the presence of hydrogen peroxide.In catalytic sulphoxidations of a series of para-substituted thioanisoles, p-XC6H4SMe, by hydrogen peroxide a good correlation has been found between the relative rates and the Hammett ?p values, indicating that direct oxygen transfer from the active oxoiron species to the sulphide is probably operative.The kinetics of the catalytic oxidation of tyrosine by hydrogen peroxide in the presence of the complex, producing the oxidative coupling dimer o,o'-dityrosine, was also studied.It is consistent with a mechanism involving the initial binding of the phenolic substrate to the active catalyst to form an intermediate complex, and its subsequent breakdown in the rate-determining step of the catalytic cycle.The results obtained in the biomimetic oxidations are compared with those of the corresponding peroxidase-catalysed reactions.
