Methionine residues ribonuclease

Vithayathil, P.J., and Richards, F.M. (1960) Modification of the methionine residue in the peptide component of ribonuclease-S./. Biol. Chem. 235, 2343-2351. 

The function, if any, of methionine sulfoxide residues in peptides or proteins is a matter of conjecture. There is no evidence that they are of any structural significance. Indeed, since various enzymes such as ribonuclease and chymotrypsin are either partially or completely inactivated by oxidation of the methionine residues (15, 16), one hesitates to suggest any functional role for the sulfoxide. However, a role in the maintenance of oxidation-reduction potential of a biological system, as suggested by Dent (3), is conceivable. 

The reaction of H atoms with bovine pancreatic ribonuclease A (RNAse A) has been studied by steady-state /-radiolysis of lipid vesicle suspensions containing RNAse A. The inactivation of RNAse A caused by interaction of H atoms with protein involved selective attack on methionine residues and was connected with release of diffusible thiyl radicals [reaction (36)] ... 

Figure 3.8. The effect of chloroplatinite on the 100 MHz H NMR spectrum of 2mM ribonuclease. The protein is initially partially unfolded, and Pt induces almost complete unfolding by binding to sulphur of methionine residues. Note the disappearance of the S-CHi resonances at A (from [117])...

The Merck3 total synthesis of ribonuclease involved coupling various peptide units to form a tetrahectapeptide (104 residues) known as S-protein. This polypeptide contains 8 cysteine and 3 methionine residues. The acetamidomethyl blocking group proved invaluable for protection of the cysteine units. 

Formation of disulfide bonds from cysteine residues is an oxidation reaction. A cysteine residue in a-amylase is oxidized at pH 8.O.818 Methionine and histidine residues are also susceptible to oxidation. Oxidation of methionine residues has been observed during storage of parathyroid hormone819 and relaxin.820 Degradation of freeze-dried ribonuclease A was ascribed to oxidation because molecular oxygen was involved in the degradation process.821... 

The S-Me methionine H resonances are shifted and broadened when PtCli binds to ribonuclease [117] (Figure 3.8). In its native state, only one residue is accessible, but all four become available for binding at low pH. Cd and Zn binding to metallothionein (mol. wt. 12000) begins at pH 2, and cysteine methylene H resonances are broadened [118]. 

Each protein has, within this general pattern, its own characteristic radical distribution. In ribonuclease, lysine exhibits a much higher activity than do the remaining amino acids. Lysine and methionine are the most heavily labeled residues in lysozyme. In myoglobin, histidine has the highest activity. Methionine is the most heavily labeled amino acid in chymotrypsinogen, as is proline in insulin. Despite the similarities, therefore, each native protein exhibits a characteristic tritium distribution. 

Signals in the aromatic region of the n.m.r. spectrum of colipase have been assigned to L-histidine residues. L-Histidine C-2 proton signals have been used in studies of the binding to ribonuclease A of H, edta and of 2 -deoxy-2 -fluorouridilyl-(3, 5 )-adenosine. L-Phenylalanine, L-tyrosine, and methionine side-chain proton resonances were used as monitors for the unfolding and stabilization of ribonuclease." ... 

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